Journal of Xenobiotics

15 pages, 301 KB

Open AccessEditor’s ChoiceReview

Endocrine-Disrupting Chemicals and Male Infertility: Mechanisms, Risks, and Regulatory Challenges

by Sofoklis Stavros, Nikolaos Kathopoulis, Efthalia Moustakli, Anastasios Potiris, Ismini Anagnostaki, Spyridon Topis, Nefeli Arkouli, Konstantinos Louis, Charalampos Theofanakis, Themos Grigoriadis, Nikolaos Thomakos and Athanasios Zikopoulos

J. Xenobiotics 2025, 15(5), 165; https://doi.org/10.3390/jox15050165 - 13 Oct 2025

Cited by 13 | Viewed by 8201

Abstract

Male reproductive health is increasingly threatened by endocrine-disrupting chemicals (EDCs), which interfere with hormonal homeostasis and reproductive physiology. Rising rates of male infertility have been linked to greater exposure to pollutants such as heavy metals, phthalates, pesticides, and bisphenol A. These compounds act [...] Read more.

Male reproductive health is increasingly threatened by endocrine-disrupting chemicals (EDCs), which interfere with hormonal homeostasis and reproductive physiology. Rising rates of male infertility have been linked to greater exposure to pollutants such as heavy metals, phthalates, pesticides, and bisphenol A. These compounds act through multiple mechanisms, including oxidative stress, apoptosis, receptor-mediated disruption of estrogenic and androgenic signaling, alterations in the hypothalamic–pituitary–gonadal (HPG) axis, and heritable epigenetic changes. Such disruptions impair key outcomes like sperm concentration, motility, morphology, DNA integrity, and steroidogenesis. Evidence from animal studies and human epidemiology consistently demonstrates these harmful effects, with biomarkers of EDC exposure correlating with reduced semen quality, hormonal imbalances, and infertility. Beyond individual health, infertility linked to EDCs carries significant social and economic costs. This review evaluates regulatory frameworks, highlights methodological challenges in risk assessment, and synthesizes mechanistic and clinical evidence. Particular attention is given to unresolved issues such as non-monotonic dose responses, mixture effects, low-dose exposures, and transgenerational impacts. Future priorities include refining biomonitoring, addressing mixture risks, and strengthening international regulation. By integrating mechanistic, clinical, and policy insights, this review underscores the urgent need for strategies to mitigate EDC-related threats to male reproductive health. Full article

(This article belongs to the Special Issue The Role of Endocrine-Disrupting Chemicals in the Human Health: 2nd Edition)

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14 pages, 691 KB

Open AccessEditor’s ChoiceArticle

Determination of Artificial Sweeteners in Commercial Beverages: Do We Know What We Are Consuming?

by Mar Castellanos and Juan M. Sanchez

J. Xenobiotics 2025, 15(5), 164; https://doi.org/10.3390/jox15050164 - 11 Oct 2025

Cited by 1 | Viewed by 5007

Abstract

Non-nutritive artificial sweeteners (NASs) are xenobiotics widely used in the food industry as sugar substitutes, since they provide few to no calories compared to sucrose. While NASs are considered safe at the acceptable daily intake (ADI) established by regulatory agencies, there is increasing [...] Read more.

Non-nutritive artificial sweeteners (NASs) are xenobiotics widely used in the food industry as sugar substitutes, since they provide few to no calories compared to sucrose. While NASs are considered safe at the acceptable daily intake (ADI) established by regulatory agencies, there is increasing controversy regarding their potential ability to promote metabolic derangements, especially to disrupt the gut microbiome balance. In this study, we analyzed a large cohort of the most commonly consumed beverages in Spain, categorizing them by the type of soda to determine the composition and content of the most frequently used NASs in the food industry. All commercial NAS formulations analyzed contained mixtures of different NASs. The NAS contents were always within regulated limits, although some samples yielded values close to these thresholds. Most soda samples analyzed contained NASs, even though the majority were not labeled as “zero sugars”, “no sugar added”, or “reduced calories”, which may mislead consumers. A preliminary statistical evaluation of the obtained results (cluster analysis) suggests that beverages can be grouped into three distinct clusters based on the total amount of NAS present in the samples. Differences in the total NAS content were significant among the three groups, with one cluster showing two- and four-fold higher levels than the others. Full article

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13 pages, 688 KB

Open AccessEditor’s ChoiceReview

Effects of Endocrine-Disrupting Chemicals in the Brain: The Example of Neurodevelopment Alterations upon Exposure In Utero to Synthetic Sex Hormones

by Charles Sultan, Laura Gaspari and Marie-Odile Soyer-Gobillard

J. Xenobiotics 2025, 15(5), 162; https://doi.org/10.3390/jox15050162 - 10 Oct 2025

Viewed by 4908

Abstract

Endocrine disruptors contaminate indoor and outdoor air, water, and food. Besides modifications of the androgen/estrogen balance, endocrine disruptors can alter thyroid function, metabolic balance, immune defenses, and brain development during fetal life, childhood, and adolescence. Among the consequences of fetal exposure to endocrine [...] Read more.

Endocrine disruptors contaminate indoor and outdoor air, water, and food. Besides modifications of the androgen/estrogen balance, endocrine disruptors can alter thyroid function, metabolic balance, immune defenses, and brain development during fetal life, childhood, and adolescence. Among the consequences of fetal exposure to endocrine disruptors, neurobehavioral disorders, particularly psychiatric disorders (for example, schizophrenia and bipolar disorder), attention deficit disorders, and mood disorders, occupy a special place. Therefore, endocrine disruptors are also neuroendocrine disruptors. This review article first summarizes the direct and transgenerational effects of endocrine disruptors. Then, data from a French national cohort of patients whose mothers were treated with synthetic hormones (estrogens and/or progestogens) during their pregnancy(ies) are used to describe the psychiatric disorders developed by children exposed in utero and the multigenerational and potentially transgenerational impacts. Full article

(This article belongs to the Special Issue The Role of Endocrine-Disrupting Chemicals in the Human Health: 2nd Edition)

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24 pages, 763 KB

Open AccessEditor’s ChoiceReview

Methylphenidate and Its Impact on Redox Balance and Behavior

by George Jîtcă, Ingrid Evelin Mehelean, Ana Natalia Maier and Carmen-Maria Jîtcă

J. Xenobiotics 2025, 15(5), 157; https://doi.org/10.3390/jox15050157 - 30 Sep 2025

Cited by 2 | Viewed by 12693

Abstract

Methylphenidate (MPH) and its active enantiomer, dexmethylphenidate, are widely prescribed as first-line therapies for attention deficit hyperactivity disorder (ADHD), yet their increasing non-medical use highlights significant clinical and toxicological challenges. MPH blocks dopamine (DAT) and norepinephrine (NET) transporters, thereby elevating synaptic catecholamine levels. [...] Read more.

Methylphenidate (MPH) and its active enantiomer, dexmethylphenidate, are widely prescribed as first-line therapies for attention deficit hyperactivity disorder (ADHD), yet their increasing non-medical use highlights significant clinical and toxicological challenges. MPH blocks dopamine (DAT) and norepinephrine (NET) transporters, thereby elevating synaptic catecholamine levels. While this underpins therapeutic efficacy, prolonged or abusive exposure has been associated with mitochondrial impairment, disrupted bioenergetics, and excessive reactive oxygen species (ROS) production, which collectively contribute to neuronal stress and long-term neurotoxicity. Growing evidence suggests that the gut–brain axis may critically influence MPH outcomes: diet-induced shifts in microbiome composition appear to regulate oxidative stress, neuroinflammation, and drug metabolism, opening potential avenues for dietary or probiotic interventions. From a forensic perspective, the detection and monitoring of MPH misuse require advanced methodologies, including enantioselective LC–MS/MS and analysis of alternative matrices such as hair or oral fluids, which enable retrospective exposure assessment and improves abuse surveillance. Despite its established therapeutic profile, MPH remains a compound with a narrow balance between clinical benefit and toxicological risk. Future directions should prioritize longitudinal human studies, biomarker identification for abuse monitoring, and the development of mitochondria-targeted therapies to minimize adverse outcomes and enhance safety in long-term treatment. Full article

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32 pages, 1701 KB

Open AccessEditor’s ChoiceReview

Healthcare Waste Toxicity: From Human Exposure to Toxic Mechanisms and Management Strategies

by Ilie Cirstea, Andrei-Flavius Radu, Ada Radu, Delia Mirela Tit and Gabriela S. Bungau

J. Xenobiotics 2025, 15(5), 155; https://doi.org/10.3390/jox15050155 - 25 Sep 2025

Cited by 10 | Viewed by 8509

Abstract

Healthcare waste (HCW) represents a growing yet frequently underestimated threat to public health, due to its complex toxicological profile. Exposure to HCW has been associated with a broad spectrum of adverse effects, including infections of bacterial, viral, or fungal origin, as well as [...] Read more.

Healthcare waste (HCW) represents a growing yet frequently underestimated threat to public health, due to its complex toxicological profile. Exposure to HCW has been associated with a broad spectrum of adverse effects, including infections of bacterial, viral, or fungal origin, as well as systemic consequences such as endocrine disruption, metabolic disturbances, and mutagenic, carcinogenic, or teratogenic outcomes. These risks are particularly elevated among healthcare professionals and waste management personnel, who are directly exposed to hazardous materials. This narrative review aims to consolidate current knowledge on the toxic potential of HCW, emphasizing the variability of risks according to waste category and point of origin. A critical reevaluation of the toxicity–health risk–waste management triad is needed to strengthen preventive and protective strategies in both clinical and waste-handling settings, and the review is therefore structured around targeted questions along this axis. Priority should be given to waste prevention, minimization, and segregation at source, as downstream treatment processes may introduce additional hazards. Each category of hazardous HCW exhibits specific mechanisms of toxicity, underlining the importance of targeted and informed management approaches. Future directions should include enhanced training for waste handlers, the development of unified regulatory frameworks, and improved international data collection and reporting systems. Strengthening these components is essential for reducing occupational and environmental health risks and ensuring safer conditions across healthcare systems. Full article

(This article belongs to the Special Issue Advances in Toxicological Research on Chemical Entities: Mechanistic Insights and Safety Profiles)

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44 pages, 1673 KB

Open AccessEditor’s ChoiceReview

Managing PFAS in Sewage Sludge: Exposure Pathways, Impacts, and Treatment Innovations

by Luoana Florentina Pascu, Valentina Andreea Petre, Ioana Antonia Cimpean, Iuliana Paun, Florinela Pirvu and Florentina Laura Chiriac

J. Xenobiotics 2025, 15(4), 135; https://doi.org/10.3390/jox15040135 - 21 Aug 2025

Cited by 15 | Viewed by 8814

Abstract

Per- and polyfluoroalkyl substances (PFAS) are a global concern due to their persistence, ubiquity, and accumulation in living organisms. Found in soils, biosolids, water, and the food chain, they pose health risks such as hormone disruption, immune damage, reproductive issues, and cancer. Regulations [...] Read more.

Per- and polyfluoroalkyl substances (PFAS) are a global concern due to their persistence, ubiquity, and accumulation in living organisms. Found in soils, biosolids, water, and the food chain, they pose health risks such as hormone disruption, immune damage, reproductive issues, and cancer. Regulations mainly target older PFAS like PFOA and PFOS, while many newer PFAS, including breakdown products, are poorly understood in terms of distribution, behavior, and toxicity. To address this complex issue, this review offers a detailed overview of human exposure to PFAS and their toxic effects. It highlights biosolids as a key, understudied source of PFAS in the environment. The review also discusses limitations of testing, missing long-term cleanup data, and regulatory issues that neglect total exposure and vulnerable populations. Additionally, it evaluates, in the specific context of biosolids management, the effectiveness, scalability, benefits, and drawbacks of various treatment technologies, such as thermal processes (pyrolysis, incineration, smoldering combustion), advanced oxidation, adsorption, hydrothermal liquefaction, and biological degradation. This work combines environmental science, toxicology, and engineering to outline PFAS management in biosolids and proposes a research and policy plan. Focusing on regulating PFAS as a group, validating real-world results, and employing adaptable treatment strategies underscores the need for a coordinated, science-based effort to reduce PFAS risks worldwide. Full article

(This article belongs to the Section Emerging Chemicals)

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35 pages, 2122 KB

Open AccessEditor’s ChoiceReview

Xenobiotic Toxicants and Particulate Matter: Effects, Mechanisms, Impacts on Human Health, and Mitigation Strategies

by Tamara Lang, Anna-Maria Lipp and Christian Wechselberger

J. Xenobiotics 2025, 15(4), 131; https://doi.org/10.3390/jox15040131 - 14 Aug 2025

Cited by 14 | Viewed by 6510

Abstract

Particulate matter (PM), a complex mixture of solid particles and liquid droplets, originates from both natural sources, such as sand, pollen, and marine salts, and anthropogenic activities, including vehicle emissions and industrial processes. While PM itself is not inherently toxic in all its [...] Read more.

Particulate matter (PM), a complex mixture of solid particles and liquid droplets, originates from both natural sources, such as sand, pollen, and marine salts, and anthropogenic activities, including vehicle emissions and industrial processes. While PM itself is not inherently toxic in all its forms, it often acts as a carrier of xenobiotic toxicants, such as heavy metals and organic pollutants, which adhere to its surface. This combination can result in synergistic toxic effects, significantly enhancing the potential harm to biological systems. Due to its small size and composition, PM can penetrate deep into the respiratory tract, acting as a physical “shuttle” that facilitates the distribution and bioavailability of toxic substances to distant organs. The omnipresence of PM in the environment leads to unavoidable and constant exposure, contributing to increased morbidity and mortality rates, particularly among vulnerable populations like the elderly, children, and individuals with pre-existing health conditions. This exposure also imposes a substantial financial burden on healthcare systems, as treating PM-related illnesses requires significant medical resources and leads to higher healthcare costs. Addressing these challenges necessitates effective mitigation strategies, including reducing PM exposure, improving air quality, and exploring novel approaches such as AI-based exposure prediction and nutritional interventions to protect public health and minimize the adverse effects of PM pollution. Full article

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42 pages, 8737 KB

Open AccessEditor’s ChoiceReview

Environmental Xenobiotics and Epigenetic Modifications: Implications for Human Health and Disease

by Ana Filipa Sobral, Andrea Cunha, Inês Costa, Mariana Silva-Carvalho, Renata Silva and Daniel José Barbosa

J. Xenobiotics 2025, 15(4), 118; https://doi.org/10.3390/jox15040118 - 13 Jul 2025

Cited by 28 | Viewed by 10611

Abstract

Environmental xenobiotics, including heavy metals, endocrine-disrupting chemicals (EDCs), pesticides, air pollutants, nano- and microplastics, mycotoxins, and phycotoxins, are widespread compounds that pose significant risks to human health. These substances, originating from industrial and agricultural activities, vehicle emissions, and household products, disrupt cellular homeostasis [...] Read more.

Environmental xenobiotics, including heavy metals, endocrine-disrupting chemicals (EDCs), pesticides, air pollutants, nano- and microplastics, mycotoxins, and phycotoxins, are widespread compounds that pose significant risks to human health. These substances, originating from industrial and agricultural activities, vehicle emissions, and household products, disrupt cellular homeostasis and contribute to a range of diseases, including cancer and neurodegenerative diseases, among others. Emerging evidence indicates that epigenetic alterations, such as abnormal deoxyribonucleic acid (DNA) methylation, aberrant histone modifications, and altered expression of non-coding ribonucleic acids (ncRNAs), may play a central role in mediating the toxic effects of environmental xenobiotics. Furthermore, exposure to these compounds during critical periods, such as embryogenesis and early postnatal stages, can induce long-lasting epigenetic alterations that increase susceptibility to diseases later in life. Moreover, modifications to the gamete epigenome can potentially lead to effects that persist across generations (transgenerational effects). Although these modifications represent significant health risks, many epigenetic alterations may be reversible through the removal of the xenobiotic trigger, offering potential for therapeutic intervention. This review explores the relationship between environmental xenobiotics and alterations in epigenetic signatures, focusing on how these changes impact human health, including their potential for transgenerational inheritance and their potential reversibility. Full article

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33 pages, 2301 KB

Open AccessEditor’s ChoiceReview

An Integrative Approach to Assessing the Impact of Mercury (Hg) on Avian Behaviour: From Molecule to Movement

by Dora Bjedov, Mirta Sudarić Bogojević, Jorge Bernal-Alviz, Goran Klobučar, Jean-Paul Bourdineaud, K. M. Aarif and Alma Mikuška

J. Xenobiotics 2025, 15(4), 117; https://doi.org/10.3390/jox15040117 - 9 Jul 2025

Cited by 7 | Viewed by 3419

Abstract

Mercury (Hg) pollution is a widespread ecological threat with sublethal effects on wildlife. Birds, due to their ecological diversity and sensitivity, serve as effective models for evaluating the behavioural impacts of Hg exposure. This review applies Tinbergen’s four questions: causation, ontogeny, function, and [...] Read more.

Mercury (Hg) pollution is a widespread ecological threat with sublethal effects on wildlife. Birds, due to their ecological diversity and sensitivity, serve as effective models for evaluating the behavioural impacts of Hg exposure. This review applies Tinbergen’s four questions: causation, ontogeny, function, and evolution, as an integrative framework. Mechanistically, Hg disrupts neuroendocrine pathways, gene expression, immune function, and hormone regulation, leading to behavioural changes such as reduced foraging, altered parental care, and impaired predator avoidance. Early-life exposure affects neural development, learning, and social behaviour into adulthood. Functionally, these changes reduce fitness by compromising reproduction and survival. Phylogenetic comparisons show interspecific variability, with piscivorous and insectivorous birds exhibiting high Hg burdens and sensitivity, linked to ecological roles and exposure. Behavioural responses often precede physiological or demographic effects, highlighting their value as early indicators. Both field and laboratory studies show that even low Hg concentrations can alter behaviour, though outcomes vary by species, life stage, and exposure route. Integrating behavioural endpoints into ecotoxicological risk assessments is essential to improve conservation strategies and understanding of sublethal pollutant effects on wildlife. Full article

(This article belongs to the Section Ecotoxicology)

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31 pages, 3799 KB

Open AccessEditor’s ChoiceArticle

Pesticide Surveillance in Fruits and Vegetables from Romanian Supply: A Data-Driven Approach

by Diana Ionela Popescu (Stegarus), Ana-Maria Nasture, Violeta-Carolina Niculescu, Corina Mihaela Oprita (Cioara) and Nicoleta Anca Șuțan (Ionescu)

J. Xenobiotics 2025, 15(4), 104; https://doi.org/10.3390/jox15040104 - 2 Jul 2025

Cited by 7 | Viewed by 4722

Abstract

The evolution of global agriculture encourages the extensive use of pesticides although significant concerns regarding their impact on human health and the environment must be considered. The present paper highlights the presence and concentrations of various pesticide residues in fruits and vegetables available [...] Read more.

The evolution of global agriculture encourages the extensive use of pesticides although significant concerns regarding their impact on human health and the environment must be considered. The present paper highlights the presence and concentrations of various pesticide residues in fruits and vegetables available on Romanian markets. A total of 74 pesticide compounds authorized for agricultural use were identified and quantified in 620 randomly selected samples spanning a wide range of horticultural products by employing the QuEChERS extraction method and liquid chromatography–mass spectrometry (LC-MS/MS). The most often detected pesticides comprised boscalid and azoxystrobin, present in 42% and 37% of apple and strawberry samples, respectively, with mean concentrations of 0.12 mg/kg and 0.09 mg/kg. In cucumbers and tomatoes, difenoconazole and acetamiprid were predominant, detected in 35% and 40% of samples, with average residue amounts of 0.08 mg/kg and 0.07 mg/kg, respectively. Statistical analysis, achieved with Python 3.13.2, the pandas library (alongside descriptive statistics), and ANOVA, revealed significant variations in residue levels based on the product type and geographic origin. Boscalid and azoxystrobin were commonly encountered in apples and strawberries while difenoconazole and acetamiprid predominated in cucumbers and tomatoes. Even though the majority of pesticide residues conformed to EU maximum residue limits (MRLs), about 6% of samples, generally from imported products, displayed some residue concentrations approaching critical thresholds, with the highest exceedance observed for chlorpyrifos and lambda-cyhalothrin at concentrations of up to 0.25 mg/kg. This research provides a comprehensive overview of pesticide residues prevalence in Romania’s fresh product supply while, at the same time, supporting consumer awareness initiatives and evidencing the critical demand for continuous monitoring and strengthened regulatory frameworks for food safety. Full article

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15 pages, 2327 KB

Open AccessEditor’s ChoiceArticle

Metabolic Costs of Emerging Contaminants: Cellular Energy Allocation in Zebrafish Embryos

by Bárbara S. Diogo, Daniela Rebelo, Sara C. Antunes and Sara Rodrigues

J. Xenobiotics 2025, 15(4), 99; https://doi.org/10.3390/jox15040099 - 29 Jun 2025

Cited by 5 | Viewed by 2036

Abstract

The use of cellular energy allocation (CEA) as a physiological energetic biomarker is useful for detecting the sublethal effects of environmental contaminants. The CEA assesses the health and energy status of organisms, serving as a reliable indicator for monitoring the health of aquatic [...] Read more.

The use of cellular energy allocation (CEA) as a physiological energetic biomarker is useful for detecting the sublethal effects of environmental contaminants. The CEA assesses the health and energy status of organisms, serving as a reliable indicator for monitoring the health of aquatic ecosystems. This study aimed to evaluate the impact of emerging contaminants already listed as a priority for monitoring in freshwater ecosystems, namely sulfamethoxazole (0.156–2.50 mg/L), trimethoprim (25.0–400 mg/L), 4-chloroaniline (5.21–20.0 mg/L), and 3,4-dichloroaniline (0.38–4.00 mg/L), on the CEA of D. rerio embryos. A standard fish embryo toxicity test was conducted, and an adaptation of the allometric scaling approach was developed through the relationship between the size and the fresh weight of the embryos. All the compounds affected the fractions of the energy reserves (total carbohydrate, lipid, and protein contents) differently, with carbohydrates being the predominant energy fraction and the most responsive indicator. Although the energy consumed showed no significant changes, the CEA was notably altered after exposure to all the contaminants, indicating a direct connection to shifts in the available energy. The CEA alterations may indicate a reallocation of energy toward detoxification, combating the stress of contaminant exposure. Energy allocation biomarkers provide a comprehensive assessment of an organism’s physiological state, which is essential for evaluating emerging contaminants’ impacts, safeguarding aquatic ecosystems, and shaping effective environmental policies. Full article

(This article belongs to the Section Ecotoxicology)

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21 pages, 1401 KB

Open AccessEditor’s ChoiceArticle

Impact of Caffeine on Aquatic Ecosystems: Assessing Trophic-Level Biological Responses

by Sara Rodrigues, Rita S. Alves and Sara C. Antunes

J. Xenobiotics 2025, 15(3), 86; https://doi.org/10.3390/jox15030086 - 3 Jun 2025

Cited by 15 | Viewed by 5733

Abstract

This study evaluates the effects of caffeine (CAF) on the bacteria Aliivibrio fischeri, the microalga Raphidocelis subcapitata, the macrophyte Lemna minor, and the larvae of Chironomus riparius, aiming to understand its environmental impact and contribution to ecological risk assessment. [...] Read more.

This study evaluates the effects of caffeine (CAF) on the bacteria Aliivibrio fischeri, the microalga Raphidocelis subcapitata, the macrophyte Lemna minor, and the larvae of Chironomus riparius, aiming to understand its environmental impact and contribution to ecological risk assessment. Bioluminescence inhibition in A. fischeri (EC₅₀ = 998.5 mg/L) and growth inhibition in R. subcapitata and L. minor (EC₅₀ = 60.1 mg/L and EC₅₀ = 649.2 mg/L, respectively) were observed. For L. minor, reduced catalase (CAT) activity and non-linear responses in glutathione S-transferases (GSTs) were recorded. No significant changes were observed in proline, malondialdehyde (MDA), and pigment contents. In C. riparius, acute mortality (LC₅₀ = 644.5 mg/L) was observed, and growth was significantly affected after 10 days of CAF exposure (EC₅₀ = 81.62 mg/L for fresh biomass). After 10 days of exposure, there was an increase in CAT activity and thiobarbituric acid reactive substances, with TBARS levels both at concentrations ≥82.64 mg/L, and a decrease in GSTs (92.18 mg/L) and acetylcholinesterase (AChE) (≤62.09 mg/L) activities of C. riparius. The results show that CAF exposure affects organisms’ metabolic and physiological functions, with varying sensitivities among species, potentially leading to ecological disturbances in aquatic ecosystems. The hazardous concentration for 5% of species was 4.42 mg/L. Long-term studies are necessary to understand the risk of caffeine under more realistic scenarios. Full article

(This article belongs to the Special Issue Environmental Toxicology and Animal Health: 2nd Edition)

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13 pages, 1287 KB

Open AccessEditor’s ChoiceArticle

QSAR Models for Predicting the Antioxidant Potential of Chemical Substances

by Sofia Ghironi, Edoardo Luca Viganò, Gianluca Selvestrel and Emilio Benfenati

J. Xenobiotics 2025, 15(3), 80; https://doi.org/10.3390/jox15030080 - 25 May 2025

Cited by 7 | Viewed by 4617

Abstract

Antioxidants are widely studied compounds with significant applications in the nutraceutical and dietary industries. To enable the rapid screening of large libraries of substances for antioxidant activity and to provide a useful tool for the initial evaluation of substances of interest with unknown [...] Read more.

Antioxidants are widely studied compounds with significant applications in the nutraceutical and dietary industries. To enable the rapid screening of large libraries of substances for antioxidant activity and to provide a useful tool for the initial evaluation of substances of interest with unknown activity, we developed Quantitative Structure–Activity Relationship (QSAR) models to predict the antioxidant potential of chemical substances. We started from a dataset of 1911 antioxidant substances, retrieved from the AODB database by selecting the DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging activity assay and the experimental value of the half-maximal inhibitory concentration. Different machine learning algorithms were applied to build regression models, and the goodness-of-fit of each model was assessed using the statistical parameters of R squared (R²), the Root-Mean-Squared Error, and the Mean Absolute Error. The Extra Trees model outperformed the other models in both internal and external validations, achieving the highest R² of 0.77 and the lowest RMSE on the test set. Gradient Boosting and eXtreme Gradient Boosting also achieved promising results with R² values of 0.76 and 0.75, respectively. Given these results, we developed an integrated method that not only outperformed the individual models, achieving an R² of 0.78 on the external test set, but also provided valuable insights into the range of predicted values. Full article

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25 pages, 2932 KB

Open AccessEditor’s ChoiceSystematic Review

Assessing the Impact of Nanoplastics in Biological Systems: Systematic Review of In Vitro Animal Studies

by Maria Viana, Fernanda S. Tonin and Carina Ladeira

J. Xenobiotics 2025, 15(3), 75; https://doi.org/10.3390/jox15030075 - 17 May 2025

Cited by 22 | Viewed by 8716

Abstract

Nanoplastic (NP) pollution has emerged as a growing concern due to its potential impact on human health, although its adverse effects on different organ systems are not yet fully understood. This systematic scoping review, conducted in accordance with international guidelines, aimed to map [...] Read more.

Nanoplastic (NP) pollution has emerged as a growing concern due to its potential impact on human health, although its adverse effects on different organ systems are not yet fully understood. This systematic scoping review, conducted in accordance with international guidelines, aimed to map the current evidence on the biological effects of NPs. In vitro animal studies assessing cellular damage caused by exposure to any type of NP were searched on PubMed, Web of Science, and Scopus. Data on primary outcomes related to genotoxicity and cytotoxicity (cell viability, oxidative stress, inflammation, DNA and cytoplasmic damage, apoptosis) were extracted from the included studies, and overall reporting quality was assessed. A total of 108 articles published between 2018 and 2024, mostly by China (54%), Spain (14%), and Italy (9%), were included. Polystyrene (PS) was the most frequently studied polymer (85%). NP sizes in solution ranged from 15 to 531 nm, with a higher prevalence in the 40–100 nm range (38%). The overall quality of studies was rated as moderate (60%), with many lacking essential details about cell culture conditions (e.g., pH of the medium, passage number, substances used). A higher frequency of negative effects from NP exposure was observed in respiratory cell lines, while immune, digestive, and hepatic cell lines showed greater resistance. Nervous, urinary, and connective tissue systems were impacted by NPs. Positively charged and smaller PS particles were consistently associated with higher toxicity across all systems. In summary, this review highlights the multifactorial nature of NP toxicity, influenced by size, surface charge, and polymer type. It also reveals a significant knowledge gap, stemming from the predominant use of immortalized monocultures exposed to commercially available PS NPs, the limited use of environmentally relevant particles, and the underutilization of advanced experimental models (e.g., organ-on-chip systems) that better mimic physiological conditions. Full article

(This article belongs to the Section Nanotoxicology and Nanopharmacology)

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38 pages, 2926 KB

Open AccessEditor’s ChoiceReview

Bioaccumulation and Trophic Transfer of Heavy Metals in Marine Fish: Ecological and Ecosystem-Level Impacts

by Andra Oros

J. Xenobiotics 2025, 15(2), 59; https://doi.org/10.3390/jox15020059 - 18 Apr 2025

Cited by 141 | Viewed by 17168

Abstract

Heavy metal contamination in marine ecosystems poses a critical environmental challenge, with significant implications for biodiversity, trophic dynamics, and human health. Marine fish are key bioindicators of heavy metal pollution because of their role in food webs and their capacity for bioaccumulation and [...] Read more.

Heavy metal contamination in marine ecosystems poses a critical environmental challenge, with significant implications for biodiversity, trophic dynamics, and human health. Marine fish are key bioindicators of heavy metal pollution because of their role in food webs and their capacity for bioaccumulation and trophic transfer. This review synthesizes current knowledge on the pathways and mechanisms of heavy metal accumulation in marine fish, focusing on factors that influence the uptake, retention, and tissue distribution. We explore the processes governing trophic transfer and biomagnification, highlighting species-specific accumulation patterns and the risks posed to apex predators, including humans. Additionally, we assess the ecological consequences of heavy metal contamination at population, community, and ecosystem levels, emphasizing its effects on fish reproduction, community structure, and trophic interactions. By integrating recent findings, this review highlights key knowledge gaps and suggests future research directions to improve environmental monitoring and risk assessment. Given the persistence and bioavailability of heavy metals in marine environments, effective pollution control strategies and sustainable fisheries management are imperative to mitigate long-term ecological and public health risks. Full article

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18 pages, 806 KB

Open AccessEditor’s ChoiceReview

Manganese Neurotoxicity: A Comprehensive Review of Pathophysiology and Inherited and Acquired Disorders

by Giuseppe Magro, Vincenzo Laterza, Federico Tosto and Angelo Torrente

J. Xenobiotics 2025, 15(2), 54; https://doi.org/10.3390/jox15020054 - 4 Apr 2025

Cited by 25 | Viewed by 13000

Abstract

Manganese (Mn) is an essential trace element and a cofactor for several key enzymes, such as mitochondrial superoxide dismutase. Consequently, it plays an important defense role against reactive oxygen species. Despite this, Mn chronic overexposure can result in a neurological disorder referred to [...] Read more.

Manganese (Mn) is an essential trace element and a cofactor for several key enzymes, such as mitochondrial superoxide dismutase. Consequently, it plays an important defense role against reactive oxygen species. Despite this, Mn chronic overexposure can result in a neurological disorder referred to as manganism, which shares some similarities with Parkinson’s disease. Mn levels seem regulated by many transporters responsible for its uptake and efflux. These transporters play an established role in many inherited disorders of Mn metabolism and neurotoxicity. Some inherited Mn metabolism disorders, caused by mutations of SLC30A10 and SLC39A14, assume crucial importance since earlier treatment results in a better prognosis. Physicians should be familiar with the clinical presentation of these disorders as the underlying cause of dystonia/parkinsonism and look for other accompanying features, such as liver disease and polycythemia, which are typically associated with SLC30A10 mutations. This review aims to highlight the currently known Mn transporters, Mn-related neurotoxicity, and its consequences, and it provides an overview of inherited and acquired disorders of Mn metabolism. Currently available treatments are also discussed, focusing on the most frequently encountered presentations. Full article

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29 pages, 1680 KB

Open AccessEditor’s ChoiceReview

The Role of Xenobiotic Caffeine on Cardiovascular Health: Promises and Challenges

by Roberto Campagna and Arianna Vignini

J. Xenobiotics 2025, 15(2), 51; https://doi.org/10.3390/jox15020051 - 31 Mar 2025

Cited by 8 | Viewed by 9702

Abstract

Cardiovascular diseases (CVDs) represent a leading cause of premature mortality and disability worldwide, with their incidence expected to rise, potentially reaching 24 million deaths per year by 2030. These multifactorial diseases, including hypertension, coronary artery disease, arrhythmia, and heart failure, are often linked [...] Read more.

Cardiovascular diseases (CVDs) represent a leading cause of premature mortality and disability worldwide, with their incidence expected to rise, potentially reaching 24 million deaths per year by 2030. These multifactorial diseases, including hypertension, coronary artery disease, arrhythmia, and heart failure, are often linked to metabolic disturbances such as diabetes, oxidative stress, endothelial dysfunction, and inflammation. Natural compounds, such as caffeine, have been explored for their potential therapeutic effects on CVDs. Caffeine, found in coffee, tea, cocoa, and various energy drinks, is a widely consumed psychoactive compound with noted analgesic and anti-inflammatory properties. Despite its long history of use, caffeine’s impact on cardiovascular health remains controversial, with both beneficial and harmful effects reported. This review examines the current literature on the effects of caffeine on cardiovascular diseases (CVDs), with an emphasis on preclinical and clinical studies, its pharmacokinetic properties, and the molecular mechanisms it modulates. There is evidence that moderate caffeine intake can be beneficial for some CVDs, such as hypertension, while for other CVDs, such as dyslipidemia, the evidence collected so far suggests that caffeine intake could be detrimental since it increases total cholesterol levels. But variability in dosage, intake patterns, and individual factors (such as genetics and diet) complicates the reliability of results. Additionally, challenges related to dose standardization and the absence of consistent clinical trial designs hinder the full utilization of caffeine in CVD treatment. Nonetheless, caffeine appears to be safe for individuals without significant cardiovascular conditions. Future research should aim for well-designed studies with precise patient cohorts and standardized methodologies to better assess caffeine’s role in CVD management. Full article

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39 pages, 4044 KB

Open AccessEditor’s ChoiceReview

The Soil–Plant Continuity of Rare Earth Elements: Insights into an Enigmatic Class of Xenobiotics and Their Interactions with Plant Structures and Processes

by Angela Martina, Lorenzo Ferroni and Elena Marrocchino

J. Xenobiotics 2025, 15(2), 46; https://doi.org/10.3390/jox15020046 - 20 Mar 2025

Cited by 17 | Viewed by 9730

Abstract

Rare earth elements (REEs) are increasingly present in the environment owing to their extensive use in modern industries, yet their interactions with plants remain poorly understood. This review explores the soil–plant continuum of REEs, focusing on their geochemical behavior in soil, the mechanisms [...] Read more.

Rare earth elements (REEs) are increasingly present in the environment owing to their extensive use in modern industries, yet their interactions with plants remain poorly understood. This review explores the soil–plant continuum of REEs, focusing on their geochemical behavior in soil, the mechanisms of plant uptake, and fractionation processes. While REEs are not essential for plant metabolism, they interact with plant structures and interfere with the normal functioning of biological macromolecules. Accordingly, the influence of REEs on the fundamental physiological functions of plants is reviewed, including calcium-mediated signalling and plant morphogenesis. Special attention is paid to the interaction of REEs with photosynthetic machinery and, particularly, the thylakoid membrane. By examining both the beneficial effects at low concentrations and toxicity at higher levels, this review provides some mechanistic insights into the hormetic action of REEs. It is recommended that future research should address knowledge gaps related to the bioavailability of REEs to plants, as well as the short- and long-range transport mechanisms responsible for REE fractionation. A better understanding of REE–plant interactions will be critical in regard to assessing their ecological impact and the potential risks in terms of agricultural and natural ecosystems, to ensure that the benefits of using REEs are not at the expense of environmental integrity or human health. Full article

(This article belongs to the Section Ecotoxicology)

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53 pages, 12782 KB

Open AccessEditor’s ChoiceReview

Brain Cytochrome P450: Navigating Neurological Health and Metabolic Regulation

by Pradeepraj Durairaj and Zixiang Leonardo Liu

J. Xenobiotics 2025, 15(2), 44; https://doi.org/10.3390/jox15020044 - 14 Mar 2025

Cited by 20 | Viewed by 12363

Abstract

Human cytochrome P450 (CYP) enzymes in the brain represent a crucial frontier in neuroscience, with far-reaching implications for drug detoxification, cellular metabolism, and the progression of neurodegenerative diseases. The brain’s complex architecture, composed of interconnected cell types and receptors, drives unique neuronal signaling [...] Read more.

Human cytochrome P450 (CYP) enzymes in the brain represent a crucial frontier in neuroscience, with far-reaching implications for drug detoxification, cellular metabolism, and the progression of neurodegenerative diseases. The brain’s complex architecture, composed of interconnected cell types and receptors, drives unique neuronal signaling pathways, modulates enzyme functions, and leads to distinct CYP gene expression and regulation patterns compared to the liver. Despite their relatively low levels of expression, brain CYPs exert significant influence on drug responses, neurotoxin susceptibility, behavior, and neurological disease risk. These enzymes are essential for maintaining brain homeostasis, mediating cholesterol turnover, and synthesizing and metabolizing neurochemicals, neurosteroids, and neurotransmitters. Moreover, they are key participants in oxidative stress responses, neuroprotection, and the regulation of inflammation. In addition to their roles in metabolizing psychotropic drugs, substances of abuse, and endogenous compounds, brain CYPs impact drug efficacy, safety, and resistance, underscoring their importance beyond traditional drug metabolism. Their involvement in critical physiological processes also links them to neuroprotection, with significant implications for the onset and progression of neurodegenerative diseases. Understanding the roles of cerebral CYP enzymes is vital for advancing neuroprotective strategies, personalizing treatments for brain disorders, and developing CNS-targeting therapeutics. This review explores the emerging roles of CYP enzymes, particularly those within the CYP1–3 and CYP46 families, highlighting their functional diversity and the pathological consequences of their dysregulation on neurological health. It also examines the potential of cerebral CYP-based biomarkers to improve the diagnosis and treatment of neurodegenerative disorders, offering new avenues for therapeutic innovation. Full article

(This article belongs to the Topic Phase I and Phase II Xenobiotic-Metabolizing Enzymes: Structure, Function, and Regulation)

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20 pages, 3608 KB

Open AccessEditor’s ChoiceArticle

Utilization of Artificial Intelligence Coupled with a High-Throughput, High-Content Platform in the Exploration of Neurodevelopmental Toxicity of Individual and Combined PFAS

by Seth D. Currie, David Blake Benson, Zhong-Ru Xie, Jia-Sheng Wang and Lili Tang

J. Xenobiotics 2025, 15(1), 24; https://doi.org/10.3390/jox15010024 - 2 Feb 2025

Cited by 12 | Viewed by 3880

Abstract

Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals used in various products, such as firefighting foams and non-stick cookware, due to their resistance to heat and degradation. However, these same properties make them persistent in the environment and human body, raising public health [...] Read more.

Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals used in various products, such as firefighting foams and non-stick cookware, due to their resistance to heat and degradation. However, these same properties make them persistent in the environment and human body, raising public health concerns. This study selected eleven PFAS commonly found in drinking water and exposed Caenorhabditis elegans to concentrations ranging from 0.1 to 200 µM to assess neurodevelopmental toxicity using a high-throughput, high-content screening (HTS) platform coupled with artificial intelligence for image analysis. Our findings showed that PFAS such as 6:2 FTS, HFPO-DA, PFBA, PFBS, PFHxA, and PFOS inhibited dopaminergic neuron activity, with fluorescence intensity reductions observed across concentrations from 0.1 to 100 µM. PFOS and PFBS also disrupted synaptic transmission, causing reduced motility and increased paralysis in aldicarb-induced assays, with the most pronounced effects at higher concentrations. These impairments in both neuron activity and synaptic function led to behavioral deficits. Notably, PFOS was one of the most toxic PFAS, affecting multiple neurodevelopmental endpoints. These results emphasize the developmental risks of PFAS exposure, highlighting the impact of both individual compounds and mixtures on neurodevelopment. This knowledge is essential for assessing PFAS-related health risks and informing mitigation strategies. Full article

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20 pages, 4429 KB

Open AccessEditor’s ChoiceArticle

Effects of Chronic Alcohol Intake on the Composition of the Ensemble of Drug-Metabolizing Enzymes and Transporters in the Human Liver

by Kari A. Gaither, Guihua Yue, Dilip Kumar Singh, Julia Trudeau, Kannapiran Ponraj, Nadezhda Y. Davydova, Philip Lazarus, Dmitri R. Davydov and Bhagwat Prasad

J. Xenobiotics 2025, 15(1), 20; https://doi.org/10.3390/jox15010020 - 31 Jan 2025

Cited by 11 | Viewed by 8494

Abstract

In this study, to better understand the mechanisms of the profound impact of alcohol consumption on drug pharmacokinetics, efficacy, and toxicity, we characterized the alcohol-induced changes in the ensemble of drug-metabolizing enzymes and transporters (DMETs) in the human liver by performing global proteomic [...] Read more.

In this study, to better understand the mechanisms of the profound impact of alcohol consumption on drug pharmacokinetics, efficacy, and toxicity, we characterized the alcohol-induced changes in the ensemble of drug-metabolizing enzymes and transporters (DMETs) in the human liver by performing global proteomic analysis of human liver microsomes from 94 donors. DMET protein levels were analyzed concerning alcohol consumption, smoking history, and sex using non-parametric tests, which were further strengthened by correlational analysis. To this end, we used a provisional index of alcohol exposure formulated based on the relative abundances of four marker proteins best correlating with the level of alcohol consumption. Alcohol-induced changes in the cytochrome P450 pool include significant increases in CYP2E1, CYP2B6, CYP2J2, and NADPH-cytochrome P450 reductase levels and the lowering of CYP1A2, CYP2C8, CYP2C9, CYP4A11, and cytochrome b₅. Changes in UDP-glucuronosyltransferase (UGT) abundances comprise elevated UGT1A6, UGT1A9, and UGT2A1, and reduced UGT1A3, UGT1A4, UGT2B7, UGT2B10, and UGT2B15 levels. Tobacco smokers showed elevated CYP1A2, UGT1A6, and UGT2B4 and reduced FMO3, FMO4, and FMO5 levels, while in females, CYP1A2, UGT2B17, and UGT2B15 levels were lower, and UGT2A3 and STS were higher compared to males. The alcohol-induced changes in the DMET ensemble at the protein level reported herein provide deep insights into how alcohol impacts drug and xenobiotic metabolism. Full article

(This article belongs to the Section Drug Therapeutics)

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31 pages, 2842 KB

Open AccessEditor’s ChoiceReview

Endocrine Disrupting Toxicity of Bisphenol A and Its Analogs: Implications in the Neuro-Immune Milieu

by Erica Buoso, Mirco Masi, Roberta Valeria Limosani, Chiara Oliviero, Sabrina Saeed, Martina Iulini, Francesca Carlotta Passoni, Marco Racchi and Emanuela Corsini

J. Xenobiotics 2025, 15(1), 13; https://doi.org/10.3390/jox15010013 - 17 Jan 2025

Cited by 40 | Viewed by 12549

Abstract

Endocrine-disrupting chemicals (EDCs) are natural or synthetic substances that are able to interfere with hormonal systems and alter their physiological signaling. EDCs have been recognized as a public health issue due to their widespread use, environmental persistence and the potential levels of long-term [...] Read more.

Endocrine-disrupting chemicals (EDCs) are natural or synthetic substances that are able to interfere with hormonal systems and alter their physiological signaling. EDCs have been recognized as a public health issue due to their widespread use, environmental persistence and the potential levels of long-term exposure with implications in multiple pathological conditions. Their reported adverse effects pose critical concerns about their use, warranting their strict regulation. This is the case of bisphenol A (BPA), a well-known EDC whose tolerable daily intake (TDI) was re-evaluated in 2023 by the European Food Safety Authority (EFSA), and the immune system has been identified as the most sensitive to BPA exposure. Increasing scientific evidence indicates that EDCs can interfere with several hormone receptors, pathways and interacting proteins, resulting in a complex, cell context-dependent response that may differ among tissues. In this regard, the neuronal and immune systems are important targets of hormonal signaling and are now emerging as critical players in endocrine disruption. Here, we use BPA and its analogs as proof-of-concept EDCs to address their detrimental effects on the immune and nervous systems and to highlight complex interrelationships within the immune–neuroendocrine network (INEN). Finally, we propose that Receptor for Activated C Kinase 1 (RACK1), an important target for EDCs and a valuable screening tool, could serve as a central hub in our toxicology model to explain bisphenol-mediated adverse effects on the INEN. Full article

(This article belongs to the Special Issue The Role of Endocrine-Disrupting Chemicals in the Human Health)

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20 pages, 4812 KB

Open AccessEditor’s ChoiceArticle

Impact of Ex Vivo Bisphenol A Exposure on Gut Microbiota Dysbiosis and Its Association with Childhood Obesity

by Gracia Luque, Pilar Ortiz, Alfonso Torres-Sánchez, Alicia Ruiz-Rodríguez, Ana López-Moreno and Margarita Aguilera

J. Xenobiotics 2025, 15(1), 14; https://doi.org/10.3390/jox15010014 - 17 Jan 2025

Cited by 9 | Viewed by 4679

Abstract

Dietary exposure to the plasticiser bisphenol A (BPA), an obesogenic and endocrine disruptor from plastic and epoxy resin industries, remains prevalent despite regulatory restriction and food safety efforts. BPA can be accumulated in humans and animals, potentially exerting differential health effects based on [...] Read more.

Dietary exposure to the plasticiser bisphenol A (BPA), an obesogenic and endocrine disruptor from plastic and epoxy resin industries, remains prevalent despite regulatory restriction and food safety efforts. BPA can be accumulated in humans and animals, potentially exerting differential health effects based on individual metabolic capacity. This pilot study examines the impact of direct ex vivo BPA exposure on the gut microbiota of obese and normal-weight children, using 16S rRNA amplicon sequencing and anaerobic culturing combined methods. Results showed that direct xenobiotic exposure induced modifications in microbial taxa relative abundance, community structure, and diversity. Specifically, BPA reduced the abundance of bacteria belonging to the phylum Bacteroidota, while taxa from the phylum Actinomycetota were promoted. Consistently, Bacteroides species were classified as sensitive to BPA, whereas bacteria belonging to the class Clostridia were identified as resistant to BPA in our culturomics analysis. Some of the altered bacterial abundance patterns were common for both the BPA-exposed groups and the obese non-exposed group in our pilot study. These findings were also corroborated in a larger cohort of children. Future research will be essential to evaluate these microbial taxa as potential biomarkers for biomonitoring the effect of BPA and its role as an obesogenic substance in children. Full article

(This article belongs to the Special Issue The Role of Endocrine-Disrupting Chemicals in the Human Health)

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22 pages, 2440 KB

Open AccessEditor’s ChoiceReview

Cardiotoxicity of Chemotherapy: A Multi-OMIC Perspective

by Yan Ma, Mandy O. J. Grootaert and Raj N. Sewduth

J. Xenobiotics 2025, 15(1), 9; https://doi.org/10.3390/jox15010009 - 8 Jan 2025

Cited by 12 | Viewed by 6613

Abstract

Chemotherapy-induced cardiotoxicity is a critical issue in cardio-oncology, as cancer treatments often lead to severe cardiovascular complications. Approximately 10% of cancer patients succumb to cardiovascular problems, with lung cancer patients frequently experiencing arrhythmias, cardiac failure, tamponade, and cardiac metastasis. The cardiotoxic effects of [...] Read more.

Chemotherapy-induced cardiotoxicity is a critical issue in cardio-oncology, as cancer treatments often lead to severe cardiovascular complications. Approximately 10% of cancer patients succumb to cardiovascular problems, with lung cancer patients frequently experiencing arrhythmias, cardiac failure, tamponade, and cardiac metastasis. The cardiotoxic effects of anti-cancer treatments manifest at both cellular and tissue levels, causing deformation of cardiomyocytes, leading to contractility issues and fibrosis. Repeated irradiation and chemotherapy increase the risk of valvular, pericardial, or myocardial diseases. Multi-OMICs analyses reveal that targeting specific pathways as well as specific protein modifications, such as ubiquitination and phosphorylation, could offer potential therapeutic alternatives to current treatments, including Angiotensin converting enzymes (ACE) inhibitors and beta-blockers that mitigate symptoms but do not prevent cardiomyocyte death, highlighting the need for more effective therapies to manage cardiovascular defects in cancer survivors. This review explores the xenobiotic nature of chemotherapy agents and their impact on cardiovascular health, aiming to identify novel biomarkers and therapeutic targets to mitigate cardiotoxicity. Full article

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26 pages, 4857 KB

Open AccessEditor’s ChoiceReview

Penetration of Microplastics and Nanoparticles Through Skin: Effects of Size, Shape, and Surface Chemistry

by Arianna Menichetti, Dario Mordini and Marco Montalti

J. Xenobiotics 2025, 15(1), 6; https://doi.org/10.3390/jox15010006 - 31 Dec 2024

Cited by 58 | Viewed by 19041

Abstract

Skin represents an effective barrier against the penetration of external agents into the human body. Nevertheless, recent research has shown that small particles, especially in the nanosized range, can not only penetrate through the skin but also work as vectors to transport active [...] Read more.

Skin represents an effective barrier against the penetration of external agents into the human body. Nevertheless, recent research has shown that small particles, especially in the nanosized range, can not only penetrate through the skin but also work as vectors to transport active molecules such as contrast agents or drugs. This knowledge has opened new perspectives on nanomedicine and controlled drug delivery. On the other hand, micro- and nanoplastics represent a form of emerging pollutants, and their concentration in the environment has been reported to drastically increase in the last years. The possible penetration of these particles through the skin has become a major concern for human health. If the actual primary toxicity of these materials is still debated, their possible role in the transport of toxic molecules through the skin, originating as secondary toxicity, is surely alarming. In this review paper, we analyze and critically discuss the most recent scientific publications to underline how these two processes, (i) the controlled delivery of bioactive molecules by micro- and nano-structures and (ii) the unwanted and uncontrolled penetration of toxic species through the skin mediated by micro- and nanoparticles, are deeply related and their efficiency is strongly affected by the nature, size, and shape of the particles. Full article

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37 pages, 641 KB

Open AccessEditor’s ChoiceReview

Prenatal Exposure to Dibutyl Phthalate and Its Negative Health Effects on Offspring: In Vivo and Epidemiological Studies

by Ana R. Quelhas, Melissa Mariana and Elisa Cairrao

J. Xenobiotics 2024, 14(4), 2039-2075; https://doi.org/10.3390/jox14040109 - 19 Dec 2024

Cited by 12 | Viewed by 5436

Abstract

Dibutyl phthalate (DBP) is a low-molecular-weight phthalate commonly found in personal care products, such as perfumes, aftershaves, and nail care items, as well as in children’s toys, pharmaceuticals, and food products. It is used to improve flexibility, make polymer products soft and malleable, [...] Read more.

Dibutyl phthalate (DBP) is a low-molecular-weight phthalate commonly found in personal care products, such as perfumes, aftershaves, and nail care items, as well as in children’s toys, pharmaceuticals, and food products. It is used to improve flexibility, make polymer products soft and malleable, and as solvents and stabilizers in personal care products. Pregnancy represents a critical period during which both the mother and the developing embryo can be significantly impacted by exposure to endocrine disruptors. This article aims to elucidate the effects of prenatal exposure to DBP on the health and development of offspring, particularly on the reproductive, neurological, metabolic, renal, and digestive systems. Extensive research has examined the effects of DBP on the male reproductive system, where exposure is linked to decreased testosterone levels, reduced anogenital distance, and male infertility. In terms of the female reproductive system, DBP has been shown to elevate serum estradiol and progesterone levels, potentially compromising egg quality. Furthermore, exposure to this phthalate adversely affects neurodevelopment and is associated with obesity, metabolic disorders, and conditions such as hypospadias. These findings highlight how urgently stronger laws prohibiting the use of phthalates during pregnancy are needed to lower the risks to the fetus’s health and the child’s development. Full article

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40 pages, 8196 KB

Open AccessFeature PaperEditor’s ChoiceReview

Impact of Endocrine Disruptors on the Genitourinary Tract

by Christophe Caneparo, Laurence Carignan, Elena Lonina, Sarah-Maude Goulet, Felix-Antoine Pellerin, Stéphane Chabaud, François Bordeleau, Stéphane Bolduc and Martin Pelletier

J. Xenobiotics 2024, 14(4), 1849-1888; https://doi.org/10.3390/jox14040099 - 2 Dec 2024

Cited by 6 | Viewed by 7708

Abstract

Over the last decades, the human species has seen an increase in the incidence of pathologies linked to the genitourinary tract. Observations in animals have allowed us to link these increases, at least in part, to changes in the environment and, in particular, [...] Read more.

Over the last decades, the human species has seen an increase in the incidence of pathologies linked to the genitourinary tract. Observations in animals have allowed us to link these increases, at least in part, to changes in the environment and, in particular, to an increasing presence of endocrine disruptors. These can be physical agents, such as light or heat; natural products, such as phytoestrogens; or chemicals produced by humans. Endocrine disruptors may interfere with the signaling pathways mediated by the endocrine system, particularly those linked to sex hormones. These factors and their general effects are presented before focusing on the male and female genitourinary tracts by describing their anatomy, development, and pathologies, including bladder and prostate cancer. Full article

(This article belongs to the Special Issue The Role of Endocrine-Disrupting Chemicals in the Human Health)

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18 pages, 1730 KB

Open AccessEditor’s ChoiceReview

Air-Pollution-Mediated Microbial Dysbiosis in Health and Disease: Lung–Gut Axis and Beyond

by Md Habibul Hasan Mazumder and Salik Hussain

J. Xenobiotics 2024, 14(4), 1595-1612; https://doi.org/10.3390/jox14040086 - 21 Oct 2024

Cited by 22 | Viewed by 7613

Abstract

Growing evidence suggests physiological and pathological functions of lung and gut microbiomes in various pathologies. Epidemiological and experimental data associate air pollution exposure with host microbial dysbiosis in the lungs and gut. Air pollution through increased reactive oxygen species generation, the disruption of [...] Read more.

Growing evidence suggests physiological and pathological functions of lung and gut microbiomes in various pathologies. Epidemiological and experimental data associate air pollution exposure with host microbial dysbiosis in the lungs and gut. Air pollution through increased reactive oxygen species generation, the disruption of epithelial barrier integrity, and systemic inflammation modulates microbial imbalance. Microbiome balance is crucial in regulating inflammation and metabolic pathways to maintain health. Microbiome dysbiosis is proposed as a potential mechanism for the air-pollution-induced modulation of pulmonary and systemic disorders. Microbiome-based therapeutic approaches are increasingly gaining attention and could have added value in promoting lung health. This review summarizes and discusses air-pollution-mediated microbiome alterations in the lungs and gut in humans and mice and elaborates on their role in health and disease. We discuss and summarize the current literature, highlight important mechanisms that lead to microbial dysbiosis, and elaborate on pathways that potentially link lung and lung microbiomes in the context of environmental exposures. Finally, we discuss the lung–liver–gut axis and its potential pathophysiological implications in air-pollution-mediated pathologies through microbial dysbiosis. Full article

(This article belongs to the Topic Disease Risks and Toxic Pathway from Environmental Chemical Exposure)

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29 pages, 7135 KB

Open AccessEditor’s ChoiceReview

Oxidative Processes and Xenobiotic Metabolism in Plants: Mechanisms of Defense and Potential Therapeutic Implications

by Caterina Vicidomini, Rosanna Palumbo, Maria Moccia and Giovanni N. Roviello

J. Xenobiotics 2024, 14(4), 1541-1569; https://doi.org/10.3390/jox14040084 - 18 Oct 2024

Cited by 77 | Viewed by 12760

Abstract

Plants are continuously exposed to environmental challenges, including pollutants, pesticides, and heavy metals, collectively termed xenobiotics. These substances induce oxidative stress by generating reactive oxygen species (ROS), which can damage cellular components such as lipids, proteins, and nucleic acids. To counteract this, plants [...] Read more.

Plants are continuously exposed to environmental challenges, including pollutants, pesticides, and heavy metals, collectively termed xenobiotics. These substances induce oxidative stress by generating reactive oxygen species (ROS), which can damage cellular components such as lipids, proteins, and nucleic acids. To counteract this, plants have evolved complex metabolic pathways to detoxify and process these harmful compounds. Oxidative stress in plants primarily arises from the overproduction of hydrogen peroxide (H₂O₂), superoxide anions (O₂^•−), singlet oxygen (¹O₂), and hydroxyl radicals (^•OH), by-products of metabolic activities such as photosynthesis and respiration. The presence of xenobiotics leads to a notable increase in ROS, which can result in cellular damage and metabolic disruption. To combat this, plants have developed a strong antioxidant defense mechanism that includes enzymatic antioxidants that work together to eliminate ROS, thereby reducing their harmful effects. In addition to enzymatic defenses, plants also synthesize various non-enzymatic antioxidants, including flavonoids, phenolic acids, and vitamins. These compounds effectively neutralize ROS and help regenerate other antioxidants, offering extensive protection against oxidative stress. The metabolism of xenobiotic substances in plants occurs in three stages: the first involves modification, which refers to the chemical alteration of xenobiotics to make them less harmful. The second involves conjugation, where the modified xenobiotics are combined with other substances to increase their solubility, facilitating their elimination from the plant. The third stage involves compartmentalization, which is the storage or isolation of conjugated xenobiotics in specific parts of the plant, helping to prevent damage to vital cellular functions. Secondary metabolites found in plants, such as alkaloids, terpenoids, and flavonoids, play a vital role in detoxification and the defense against oxidative stress. Gaining a deeper understanding of the oxidative mechanisms and the pathways of xenobiotic metabolism in plants is essential, as this knowledge can lead to the formulation of plant-derived strategies aimed at alleviating the effects of environmental pollution and enhancing human health by improving detoxification and antioxidant capabilities, as discussed in this review. Full article

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17 pages, 2404 KB

Open AccessEditor’s ChoiceArticle

In Vitro and In Vivo Genotoxicity of Polystyrene Microplastics: Evaluation of a Possible Synergistic Action with Bisphenol A

by Alfredo Santovito, Mattia Lambertini and Alessandro Nota

J. Xenobiotics 2024, 14(4), 1415-1431; https://doi.org/10.3390/jox14040079 - 8 Oct 2024

Cited by 17 | Viewed by 4875

Abstract

The ubiquitous presence of plastics represents a global threat for all ecosystems and human health. In this study, we evaluated, in vitro and in vivo, the genotoxic potential of different concentrations of polystyrene microplastics (PS-MPs) and their possible synergistic interactions with bisphenol-A (BPA). [...] Read more.

The ubiquitous presence of plastics represents a global threat for all ecosystems and human health. In this study, we evaluated, in vitro and in vivo, the genotoxic potential of different concentrations of polystyrene microplastics (PS-MPs) and their possible synergistic interactions with bisphenol-A (BPA). For the in vitro and the in vivo assays, we used human lymphocytes and hemocytes from Lymnaea stagnalis, respectively. The genomic damage was evaluated by the micronucleus assay, and differences in eggs laid and growth of L. stagnalis were also evaluated. In human lymphocytes, PS-MPs alone at the concentration of 200 μg/mL and in association with BPA 0.100 µg/mL significantly increased the frequencies of micronuclei and nuclear buds, indicating a possible in vitro genotoxic additive action of these two compounds. Vice versa, PS-MPs did not result in genotoxicity in hemocytes. Our results indicated that PS-MPs have genotoxic properties only in vitro and at a concentration of 200 µg/mL; moreover, this compound could intensify the genomic damage when tested with BPA, indicating possible cumulative effects. Finally, PS significantly reduced the growth and the number of laid eggs in L. stagnalis. Full article

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28 pages, 1395 KB

Open AccessEditor’s ChoiceReview

Polyphenols Regulate the Activity of Endocrine-Disrupting Chemicals, Having Both Positive and Negative Effects

by Eleonora Leti Maggio, Carlotta Zucca, Martina Grande, Raffaele Carrano, Antonio Infante, Riccardo Bei, Valeria Lucarini, Fernando De Maio, Chiara Focaccetti, Camilla Palumbo, Stefano Marini, Elisabetta Ferretti, Loredana Cifaldi, Laura Masuelli, Monica Benvenuto and Roberto Bei

J. Xenobiotics 2024, 14(4), 1378-1405; https://doi.org/10.3390/jox14040077 - 2 Oct 2024

Cited by 13 | Viewed by 6251

Abstract

Endocrine-disrupting chemicals (EDCs) are chemical substances that can interfere with any hormone action. They are categorized according to origin and use, such as industrial chemicals like polychlorinated biphenyls (PCBs) and polybrominated biphenyls (PBBs), plastics like bisphenol A (BPA), plasticizers like phthalates, pesticides like [...] Read more.

Endocrine-disrupting chemicals (EDCs) are chemical substances that can interfere with any hormone action. They are categorized according to origin and use, such as industrial chemicals like polychlorinated biphenyls (PCBs) and polybrominated biphenyls (PBBs), plastics like bisphenol A (BPA), plasticizers like phthalates, pesticides like dichlorodiphenyltrichloroethane (DDT), fungicides like vinclozolin, and pharmaceuticals like diethylstilbestrol (DES). Natural EDCs, such as phytoestrogens, are present in the diet of both humans and animals. Polyphenols are a large group of natural compounds derived from plants and are found in beverages and food. They are grouped based on their chemical structure into flavonoids and nonflavonoids and are reported to have many beneficial effects on health, including, but not limited to, anticancer, antioxidant, and anti-inflammatory effects. Moreover, polyphenols have both pro- and antioxidant characteristics, and due to their antioxidant and anti-inflammatory potential, they presumably have a protective effect against damage induced by EDCs. However, polyphenols may act as EDCs. In this review, we report that polyphenols regulate the activity of EDCs, having both positive and negative effects. Hence, a better understanding of the associations between EDCs and polyphenols will allow the establishment of improved approaches to protect human health from EDCs. Full article

(This article belongs to the Special Issue The Role of Endocrine-Disrupting Chemicals in the Human Health)

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35 pages, 8651 KB

Open AccessEditor’s ChoiceReview

How Pharmaceutical Residues Occur, Behave, and Affect the Soil Environment

by Gabriel Pérez-Lucas and Simón Navarro

J. Xenobiotics 2024, 14(4), 1343-1377; https://doi.org/10.3390/jox14040076 - 1 Oct 2024

Cited by 37 | Viewed by 9249

Abstract

Many pharmaceuticals (PhMs), compounds for the treatment or prevention of diseases in humans and animals, have been identified as pollutants of emerging concern (PECs) due to their wide environmental distribution and potential adverse impact on nontarget organisms and populations. They are often found [...] Read more.

Many pharmaceuticals (PhMs), compounds for the treatment or prevention of diseases in humans and animals, have been identified as pollutants of emerging concern (PECs) due to their wide environmental distribution and potential adverse impact on nontarget organisms and populations. They are often found at significant levels in soils due to the continuous release of effluent and sludge from wastewater treatment plants (WWTPs), the release of which occurs much faster than the removal of PhMs. Although they are generally present at low environmental concentrations, conventional wastewater treatment cannot successfully remove PhMs from influent streams or biosolids. In addition, the soil application of animal manure can result in the pollution of soil, surface water, and groundwater with PhMs through surface runoff and leaching. In arid and semiarid regions, irrigation with reclaimed wastewater and the soil application of biosolids are usual agricultural practices, resulting in the distribution of a wide number of PhMs in agricultural soils. The ability to accurately study the fate of PhMs in soils is critical for careful risk evaluation associated with wastewater reuse or biosolid return to the environment. The behavior and fate of PhMs in soils are determined by a number of processes, including adsorption/desorption (accumulation) to soil colloids, biotic (biodegradation) and abiotic (chemical and photochemical degradation) degradation, and transfer (movement) through the soil profile. The sorption/desorption of PhMs in soils is the main determinant of the amount of organic chemicals taken up by plant roots. The magnitude of this process depends on several factors, such as crop type, the physicochemical properties of the compound, environmental properties, and soil–plant characteristics. PhMs are assumed to be readily bioavailable in soil solutions for uptake by plants, and such solutions act as carriers to transport PhMs into plants. Determining microbial responses under exposure conditions can assist in elucidating the impact of PhMs on soil microbial activity and community size. For all of the above reasons, soil remediation is critical when soil pollutants threaten the environment. Full article

(This article belongs to the Section Emerging Chemicals)

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25 pages, 7423 KB

Open AccessEditor’s ChoiceReview

Lubricant Strategies in Osteoarthritis Treatment: Transitioning from Natural Lubricants to Drug Delivery Particles with Lubricant Properties

by Agnese Fragassi, Antonietta Greco and Roberto Palomba

J. Xenobiotics 2024, 14(3), 1268-1292; https://doi.org/10.3390/jox14030072 - 19 Sep 2024

Cited by 16 | Viewed by 6406

Abstract

Osteoarthritis (OA) is a debilitating joint disease characterized by cartilage degradation, leading to pain and functional impairment. A key contributor to OA progression is the decline in cartilage lubrication. In physiological conditions, synovial fluid (SF) macromolecules like hyaluronic acid (HA), phospholipids, and lubricin [...] Read more.

Osteoarthritis (OA) is a debilitating joint disease characterized by cartilage degradation, leading to pain and functional impairment. A key contributor to OA progression is the decline in cartilage lubrication. In physiological conditions, synovial fluid (SF) macromolecules like hyaluronic acid (HA), phospholipids, and lubricin play a crucial role in the boundary lubrication of articular cartilage. In early OA, cartilage damage triggers inflammation, altering SF composition and compromising the lubrication layer. This increases friction between mating interfaces, worsening cartilage degradation and local inflammation. Therefore, early-stage restoration of lubrication (by injecting in the joint different classes of compounds and formulations) could alleviate, and potentially reverse, OA progression. In the light of this, a broad variety of lubricants have been investigated for their ability to reduce friction in OA joints and promote cartilage repair in clinical and preclinical studies. This review examines recent advancements in lubricant-based therapy for OA, focusing on natural, bioinspired, and alternative products. Starting from the currently applied therapy, mainly based on natural lubricants as HA, we will present their modified versions, either in hydrogel form or with specific biomimetic moieties with the aim of reducing their clearance from the joint and of enhancing their lubricating properties. Finally, the most advanced and recent formulation, represented by alternative strategies, will be proposed. Particular emphasis will be placed on those ones involving new types of hydrogels, microparticles, nanoparticles, and liposomes, which are currently under investigation in preclinical studies. The potential application of particles and liposomes could foster the transition from natural lubricants to Drug Delivery Systems (DDSs) with lubricant features; transition which could provide more complete OA treatments, by simultaneously providing lubrication replacement and sustained release of different payloads and active agents directly at the joint level. Within each category, we will examine relevant preclinical studies, highlighting challenges and future prospects. Full article

(This article belongs to the Section Nanotoxicology and Nanopharmacology)

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46 pages, 5926 KB

Open AccessEditor’s ChoiceReview

Precision Nanomedicine with Bio-Inspired Nanosystems: Recent Trends and Challenges in Mesenchymal Stem Cells Membrane-Coated Bioengineered Nanocarriers in Targeted Nanotherapeutics

by Mirza Salman Baig, Anas Ahmad, Rijawan Rajjak Pathan and Rakesh Kumar Mishra

J. Xenobiotics 2024, 14(3), 827-872; https://doi.org/10.3390/jox14030047 - 24 Jun 2024

Cited by 24 | Viewed by 6735

Abstract

In the recent past, the formulation and development of nanocarriers has been elaborated into the broader fields and opened various avenues in their preclinical and clinical applications. In particular, the cellular membrane-based nanoformulations have been formulated to surpass and surmount the limitations and [...] Read more.

In the recent past, the formulation and development of nanocarriers has been elaborated into the broader fields and opened various avenues in their preclinical and clinical applications. In particular, the cellular membrane-based nanoformulations have been formulated to surpass and surmount the limitations and restrictions associated with naïve or free forms of therapeutic compounds and circumvent various physicochemical and immunological barriers including but not limited to systemic barriers, microenvironmental roadblocks, and other cellular or subcellular hinderances—which are quite heterogeneous throughout the diseases and patient cohorts. These limitations in drug delivery have been overcome through mesenchymal cells membrane-based precision therapeutics, where these interventions have led to the significant enhancements in therapeutic efficacies. However, the formulation and development of nanocarriers still focuses on optimization of drug delivery paradigms with a one-size-fits-all resolutions. As mesenchymal stem cell membrane-based nanocarriers have been engineered in highly diversified fashions, these are being optimized for delivering the drug payloads in more and better personalized modes, entering the arena of precision as well as personalized nanomedicine. In this Review, we have included some of the advanced nanocarriers which have been designed and been utilized in both the non-personalized as well as precision applicability which can be employed for the improvements in precision nanotherapeutics. In the present report, authors have focused on various other aspects of the advancements in stem cells membrane-based nanoparticle conceptions which can surmount several roadblocks and barriers in drug delivery and nanomedicine. It has been suggested that well-informed designing of these nanocarriers will lead to appreciable improvements in the therapeutic efficacy in therapeutic payload delivery applications. These approaches will also enable the tailored and customized designs of MSC-based nanocarriers for personalized therapeutic applications, and finally amending the patient outcomes. Full article

(This article belongs to the Section Drug Therapeutics)

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19 pages, 353 KB

Open AccessEditor’s ChoiceReview

Microbial Symbiont-Based Detoxification of Different Phytotoxins and Synthetic Toxic Chemicals in Insect Pests and Pollinators

by Olivia Kline and Neelendra K. Joshi

J. Xenobiotics 2024, 14(2), 753-771; https://doi.org/10.3390/jox14020043 - 4 Jun 2024

Cited by 18 | Viewed by 5964

Abstract

Insects are the most diverse form of life, and as such, they interact closely with humans, impacting our health, economy, and agriculture. Beneficial insect species contribute to pollination, biological control of pests, decomposition, and nutrient cycling. Pest species can cause damage to agricultural [...] Read more.

Insects are the most diverse form of life, and as such, they interact closely with humans, impacting our health, economy, and agriculture. Beneficial insect species contribute to pollination, biological control of pests, decomposition, and nutrient cycling. Pest species can cause damage to agricultural crops and vector diseases to humans and livestock. Insects are often exposed to toxic xenobiotics in the environment, both naturally occurring toxins like plant secondary metabolites and synthetic chemicals like herbicides, fungicides, and insecticides. Because of this, insects have evolved several mechanisms of resistance to toxic xenobiotics, including sequestration, behavioral avoidance, and enzymatic degradation, and in many cases had developed symbiotic relationships with microbes that can aid in this detoxification. As research progresses, the important roles of these microbes in insect health and function have become more apparent. Bacterial symbionts that degrade plant phytotoxins allow host insects to feed on otherwise chemically defended plants. They can also confer pesticide resistance to their hosts, especially in frequently treated agricultural fields. It is important to study these interactions between insects and the toxic chemicals they are exposed to in order to further the understanding of pest insect resistance and to mitigate the negative effect of pesticides on nontarget insect species like Hymenopteran pollinators. Full article

(This article belongs to the Special Issue Environmental Toxicology and Animal Health)

36 pages, 1996 KB

Open AccessEditor’s ChoiceReview

A Review on Fluoroquinolones’ Toxicity to Freshwater Organisms and a Risk Assessment

by Marianna Pauletto and Marco De Liguoro

J. Xenobiotics 2024, 14(2), 717-752; https://doi.org/10.3390/jox14020042 - 4 Jun 2024

Cited by 32 | Viewed by 6769

Abstract

Fluoroquinolones (FQs) have achieved significant success in both human and veterinary medicine. However, regulatory authorities have recommended limiting their use, firstly because they can have disabling side effects; secondly, because of the need to limit the spread of antibiotic resistance. This review addresses [...] Read more.

Fluoroquinolones (FQs) have achieved significant success in both human and veterinary medicine. However, regulatory authorities have recommended limiting their use, firstly because they can have disabling side effects; secondly, because of the need to limit the spread of antibiotic resistance. This review addresses another concerning consequence of the excessive use of FQs: the freshwater environments contamination and the impact on non-target organisms. Here, an overview of the highest concentrations found in Europe, Asia, and the USA is provided, the sensitivity of various taxa is presented through a comparison of the lowest EC_50s from about a hundred acute toxicity tests, and primary mechanisms of FQ toxicity are described. A risk assessment is conducted based on the estimation of the Predicted No Effect Concentration (PNEC). This is calculated traditionally and, in a more contemporary manner, by constructing a normalized Species Sensitivity Distribution curve. The lowest individual HC5 (6.52 µg L⁻¹) was obtained for levofloxacin, followed by ciprofloxacin (7.51 µg L⁻¹), sarafloxacin and clinafloxacin (12.23 µg L⁻¹), and ofloxacin (17.12 µg L⁻¹). By comparing the calculated PNEC with detected concentrations, it is evident that the risk cannot be denied: the potential impact of FQs on freshwater ecosystems is a further reason to minimize their use. Full article

(This article belongs to the Special Issue Environmental Toxicology and Animal Health)

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16 pages, 2890 KB

Open AccessEditor’s ChoiceArticle

Bioaccumulation of Organic and Inorganic Pollutants in Fish from Thermaikos Gulf: Preliminary Human Health Risk Assessment Assisted by a Computational Approach

by Konstantinos M. Kasiotis, Effrosyni Zafeiraki, Electra Manea-Karga, Demetrios Kouretas, Fotis Tekos, Zoi Skaperda, Nikolaos Doumpas and Kyriaki Machera

J. Xenobiotics 2024, 14(2), 701-716; https://doi.org/10.3390/jox14020041 - 1 Jun 2024

Cited by 6 | Viewed by 4073

Abstract

The monitoring of contaminants in fish species is pivotal for fishes’ health and reproduction, as well as for human health. In the specific work, three major categories of contaminants, pesticides, pharmaceuticals, and macro and trace elements, were investigated in two major fish species, [...] Read more.

The monitoring of contaminants in fish species is pivotal for fishes’ health and reproduction, as well as for human health. In the specific work, three major categories of contaminants, pesticides, pharmaceuticals, and macro and trace elements, were investigated in two major fish species, Dicentrarchus labrax and Solea solea, collected from Thermaikos Gulf, in Greece. To achieve this goal, three analytical methods using LC-MS/MS, GC-MS/MS, and ICP-MS were developed, validated, and applied to the collected fish samples. The results indicated a very low prevalence of caffeine and acetaminophen, both not exceeding 3.8 μg/kg fish. Similarly, thiabendazole, cypermethrin, and tricyclazole (pesticides) were found in a concentration range of 0.9 to 13.7 μg/kg fish, while in one D. labrax sample, traces of the metabolite of organochlorine pesticide DDT, o,p’-DDE were detected. Al, Mn, Fe, Zn, and Sr were the predominant trace elements in a concentration range of 500–20,000 μg/kg fish. Macro elements levels varied from 280 to 5405 mg/kg fish. Health risk assessment did not unveil an unacceptable risk for the human health of adults, apart from one sample presenting Hg above the regulatory levels. On the contrary, for children, the calculated hazard quotient values for Hg in all cases and for two As detections were higher than the threshold value of 1, indicating a potential risk. Full article

(This article belongs to the Special Issue Legacy and Emerging Pollutants and Their Effects through the Lens of Environmental Management)

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36 pages, 3709 KB

Open AccessEditor’s ChoiceReview

Bamboo-Based Biochar: A Still Too Little-Studied Black Gold and Its Current Applications

by Silvana Alfei and Omar Ginoble Pandoli

J. Xenobiotics 2024, 14(1), 416-451; https://doi.org/10.3390/jox14010026 - 20 Mar 2024

Cited by 31 | Viewed by 12086

Abstract

Biochar (BC), also referred to as “black gold”, is a carbon heterogeneous material rich in aromatic systems and minerals, preparable by the thermal decomposition of vegetable and animal biomasses in controlled conditions and with clean technology. Due to its adsorption ability and presence [...] Read more.

Biochar (BC), also referred to as “black gold”, is a carbon heterogeneous material rich in aromatic systems and minerals, preparable by the thermal decomposition of vegetable and animal biomasses in controlled conditions and with clean technology. Due to its adsorption ability and presence of persistent free radicals (PFRs), BC has demonstrated, among other uses, great potential in the removal of environmental organic and inorganic xenobiotics. Bamboo is an evergreen perennial flowering plant characterized by a short five-year growth period, fast harvesting, and large production in many tropical and subtropical countries worldwide, thus representing an attractive, low-cost, eco-friendly, and renewable bioresource for producing BC. Due to their large surface area and increased porosity, the pyrolyzed derivatives of bamboo, including bamboo biochar (BBC) or activated BBC (ABBC), are considered great bio-adsorbent materials for removing heavy metals, as well as organic and inorganic contaminants from wastewater and soil, thus improving plant growth and production yield. Nowadays, the increasing technological applications of BBC and ABBC also include their employment as energy sources, to catalyze chemical reactions, to develop thermoelectrical devices, as 3D solar vapor-generation devices for water desalination, and as efficient photothermal-conversion devices. Anyway, although it has great potential as an alternative biomass to wood to produce BC, thus paving the way for new bio- and circular economy solutions, the study of bamboo-derived biomasses is still in its infancy. In this context, the main scope of this review was to support an increasing production of BBC and ABBC and to stimulate further studies about their possible applications, thus enlarging the current knowledge about these materials and allowing their more rational, safer, and optimized application. To this end, after having provided background concerning BC, its production methods, and its main applications, we have reviewed and discussed the main studies on BBC and ABBC and their applications reported in recent years. Full article

(This article belongs to the Special Issue Feature Papers in Ecotoxicology)

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18 pages, 2303 KB

Open AccessEditor’s ChoiceArticle

Assessing Chemical Intolerance in Parents Predicts the Risk of Autism and ADHD in Their Children

by Raymond F. Palmer, David Kattari, Rodolfo Rincon and Claudia S. Miller

J. Xenobiotics 2024, 14(1), 350-367; https://doi.org/10.3390/jox14010022 - 5 Mar 2024

Cited by 6 | Viewed by 14997

Abstract

Background: We sought to replicate our 2015 findings linking chemical intolerance in parents with the risk of their children developing autism and/or ADHD. Drawing upon our 2021 discovery of a strong association between chemical intolerance and mast cells, we propose an explanation for [...] Read more.

Background: We sought to replicate our 2015 findings linking chemical intolerance in parents with the risk of their children developing autism and/or ADHD. Drawing upon our 2021 discovery of a strong association between chemical intolerance and mast cells, we propose an explanation for this link. Methods: In a population-based survey of U.S. adults, we used the internationally validated Quick Environmental Exposure and Sensitivity Inventory (QEESI) to assess symptom severity and chemical intolerance. Parents were asked how many of their biological children had been diagnosed with autism and/or ADHD. Results: Parents with chemical intolerance scores in the top versus bottom tenth percentile had 5.7 times the risk of reporting a child with autism and 2.1 times for ADHD. Conclusions: High chemical intolerance scores among parents of children with autism, coupled with our 2021 discovery of mast cell activation as a plausible biomechanism for chemical intolerance, suggest that (1) the QEESI can identify individuals at increased risk, (2) environmental counseling may reduce personal exposures and risk, and (3) the global rise in autism and ADHD may be due to fossil-fuel-derived and biogenic toxicants epigenetically “turning on” or “turning off” critical mast cell genes that can be transmitted transgenerationally. It is important to note that this study was observational in nature; as such, further research is needed using controlled trials to confirm causality and explore the proposed mechanism. Full article

(This article belongs to the Special Issue Environmental Conditions and Autism Spectrum Disorders)

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13 pages, 1983 KB

Open AccessFeature PaperEditor’s ChoiceArticle

Pyriproxyfen Contamination in Daphnia magna: Identifying Early Warning Biomarkers

by Beatriz Salesa, Javier Torres-Gavilá, María Dolores Ferrando-Rodrigo and Encarnación Sancho

J. Xenobiotics 2024, 14(1), 214-226; https://doi.org/10.3390/jox14010013 - 2 Feb 2024

Cited by 10 | Viewed by 3291

Abstract

Pyriproxyfen is an insecticide currently employed in numerous countries for the management of agricultural and indoor pests. Several studies indicate that this insecticide has been detected in multiple rivers, with concentrations reaching as high as 99.59 ng/L in the Júcar River in Spain. [...] Read more.

Pyriproxyfen is an insecticide currently employed in numerous countries for the management of agricultural and indoor pests. Several studies indicate that this insecticide has been detected in multiple rivers, with concentrations reaching as high as 99.59 ng/L in the Júcar River in Spain. Therefore, the determination of some biochemical and genetic effects of this insecticide on aquatic organisms could serve as an early warning mechanism to identify potential disruptions in various biomarkers. Based on this, Daphnia magna organisms were exposed to pyriproxyfen sublethal concentrations for 21 days. Some biochemical parameters, including cholesterol, triglycerides, glucose, lactate, and LDH activity, were determined. Additionally, some genetic biomarkers associated with oxidative stress, heat shock proteins, lipid metabolism, hemoglobin, metallothioneins, and vitellogenin synthesis were evaluated in daphnids exposed to the insecticide for 21 days. LDH activity increased significantly in those daphnids exposed to the highest insecticide concentration (14.02 µg/L), while cholesterol levels decreased significantly. In contrast, glucose, total proteins, and triglycerides remained unaffected in D. magna exposed to pyriproxyfen. On the other hand, exposure to the insecticide led to notable alterations in gene expression among individuals. Specifically, genes associated with lipid metabolism and reproduction exhibited a significant reduction in gene expression. Fabd expression was decreased by approximately 20% in exposed daphnids, while vtg expression was suppressed as much as 80% when compared to control values. Furthermore, it was observed that the hgb1 and hgb2 genes, associated with hemoglobin synthesis, exhibited significant overexpression. Notably, the dysfunction observed in both hemoglobin genes was linked to an increase in pigmentation in Daphnia magna during the course of the experiment. These alterations in gene expression could serve as effective indicators of early contamination even at low pesticide concentrations. Full article

(This article belongs to the Special Issue Legacy and Emerging Pollutants and Their Effects through the Lens of Environmental Management)

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10 pages, 1056 KB

Open AccessEditor’s ChoiceArticle

Early Female Transgender Identity after Prenatal Exposure to Diethylstilbestrol: Report from a French National Diethylstilbestrol (DES) Cohort

by Laura Gaspari, Marie-Odile Soyer-Gobillard, Scott Kerlin, Françoise Paris and Charles Sultan

J. Xenobiotics 2024, 14(1), 166-175; https://doi.org/10.3390/jox14010010 - 12 Jan 2024

Cited by 5 | Viewed by 34558

Abstract

Diagnostic of transsexualism and gender incongruence are terms to describe individuals whose self-identity does not match their sex assignment at birth. A transgender woman is an individual assigned male at birth (AMAB) on the basis of the external or internal genitalia who identifies [...] Read more.

Diagnostic of transsexualism and gender incongruence are terms to describe individuals whose self-identity does not match their sex assignment at birth. A transgender woman is an individual assigned male at birth (AMAB) on the basis of the external or internal genitalia who identifies and lives as a woman. In recent decades, a significant increase in the number of transgender people has been reported. Although, its etiology is unknown, biological, anatomical, genetic, environmental and cultural factors have been suggested to contribute to gender variation. In XY animals, it has been shown that environmental endocrine disruptors, through their anti-androgenic activity, induce a female identity. In this work, we described four XY individuals who were exposed in utero to the xenoestrogen diethylstilbesterol (DES) and were part of the French HHORAGES cohort. They all reported a female transgender identity starting from childhood and adolescence. This high prevalence of male to female transgenderism (1.58%) in our cohort of 253 DES sons suggests that exposure to chemicals with xenoestrogen activity during fetal life may affect the male sex identity and behavior. Full article

(This article belongs to the Special Issue The Role of Endocrine-Disrupting Chemicals in the Human Health)

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36 pages, 2294 KB

Open AccessEditor’s ChoiceReview

Bisphenol A (BPA) and Cardiovascular or Cardiometabolic Diseases

by Jeong-Hun Kang, Daisuke Asai and Riki Toita

J. Xenobiotics 2023, 13(4), 775-810; https://doi.org/10.3390/jox13040049 - 5 Dec 2023

Cited by 43 | Viewed by 12059

Abstract

Bisphenol A (BPA; 4,4′-isopropylidenediphenol) is a well-known endocrine disruptor. Most human exposure to BPA occurs through the consumption of BPA-contaminated foods. Cardiovascular or cardiometabolic diseases such as diabetes, obesity, hypertension, acute kidney disease, chronic kidney disease, and heart failure are the leading causes [...] Read more.

Bisphenol A (BPA; 4,4′-isopropylidenediphenol) is a well-known endocrine disruptor. Most human exposure to BPA occurs through the consumption of BPA-contaminated foods. Cardiovascular or cardiometabolic diseases such as diabetes, obesity, hypertension, acute kidney disease, chronic kidney disease, and heart failure are the leading causes of death worldwide. Positive associations have been reported between blood or urinary BPA levels and cardiovascular or cardiometabolic diseases. BPA also induces disorders or dysfunctions in the tissues associated with these diseases through various cell signaling pathways. This review highlights the literature elucidating the relationship between BPA and various cardiovascular or cardiometabolic diseases and the potential mechanisms underlying BPA-mediated disorders or dysfunctions in tissues such as blood vessels, skeletal muscle, adipose tissue, liver, pancreas, kidney, and heart that are associated with these diseases. Full article

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14 pages, 2145 KB

Open AccessEditor’s ChoiceArticle

Micro and Nanoplastic Contamination and Its Effects on Freshwater Mussels Caged in an Urban Area

by François Gagné, Eva Roubeau-Dumont, Chantale André and Joëlle Auclair

J. Xenobiotics 2023, 13(4), 761-774; https://doi.org/10.3390/jox13040048 - 5 Dec 2023

Cited by 16 | Viewed by 4724

Abstract

Plastic-based contamination has become a major cause of concern as it pervades many environments such as air, water, sediments, and soils. This study sought to examine the presence of microplastics (MPs) and nanoplastics (NPs) in freshwater mussels placed at rainfall/street runoff overflows, downstream [...] Read more.

Plastic-based contamination has become a major cause of concern as it pervades many environments such as air, water, sediments, and soils. This study sought to examine the presence of microplastics (MPs) and nanoplastics (NPs) in freshwater mussels placed at rainfall/street runoff overflows, downstream (15 km) of the city centre of Montréal, and 8 km downstream of a municipal effluent dispersion plume. MPs and NPs were determined using flow cytometry and size exclusion chromatography using fluorescence detection. Following 3 months of exposure during the summer season, mussels contained elevated amounts of both MPs and NPs. The rainfall overflow and downstream of the city centre were the most contaminated sites. Lipid peroxidation, metallothioneins, and protein aggregates (amyloids) were significantly increased at the most contaminated sites and were significantly correlated with NPs in tissues. Based on the levels of MPs and NPs in mussels exposed to municipal effluent, wastewater treatment plants appear to mitigate plastic contamination albeit not completely. In conclusion, the data support the hypothesis that mussels placed in urbanized areas are more contaminated by plastics, which are associated with oxidative damage. The highest responses observed at the overflow site suggest that tire wear and/or asphalt (road) erosion MPs/NPs represent important sources of contamination for the aquatic biota. Full article

(This article belongs to the Topic Plastics, Water-Soluble Polymers and Rubberized Materials: Ecotoxicological Aspects in the Aquatic Environments)

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32 pages, 2761 KB

Open AccessEditor’s ChoiceReview

Microbial Exudates as Biostimulants: Role in Plant Growth Promotion and Stress Mitigation

by Mariya Ansari, B. Megala Devi, Ankita Sarkar, Anirudha Chattopadhyay, Lovkush Satnami, Pooraniammal Balu, Manoj Choudhary, Muhammad Adnan Shahid and A. Abdul Kader Jailani

J. Xenobiotics 2023, 13(4), 572-603; https://doi.org/10.3390/jox13040037 - 1 Oct 2023

Cited by 70 | Viewed by 12792

Abstract

Microbes hold immense potential, based on the fact that they are widely acknowledged for their role in mitigating the detrimental impacts of chemical fertilizers and pesticides, which were extensively employed during the Green Revolution era. The consequence of this extensive use has been [...] Read more.

Microbes hold immense potential, based on the fact that they are widely acknowledged for their role in mitigating the detrimental impacts of chemical fertilizers and pesticides, which were extensively employed during the Green Revolution era. The consequence of this extensive use has been the degradation of agricultural land, soil health and fertility deterioration, and a decline in crop quality. Despite the existence of environmentally friendly and sustainable alternatives, microbial bioinoculants encounter numerous challenges in real-world agricultural settings. These challenges include harsh environmental conditions like unfavorable soil pH, temperature extremes, and nutrient imbalances, as well as stiff competition with native microbial species and host plant specificity. Moreover, obstacles spanning from large-scale production to commercialization persist. Therefore, substantial efforts are underway to identify superior solutions that can foster a sustainable and eco-conscious agricultural system. In this context, attention has shifted towards the utilization of cell-free microbial exudates as opposed to traditional microbial inoculants. Microbial exudates refer to the diverse array of cellular metabolites secreted by microbial cells. These metabolites enclose a wide range of chemical compounds, including sugars, organic acids, amino acids, peptides, siderophores, volatiles, and more. The composition and function of these compounds in exudates can vary considerably, depending on the specific microbial strains and prevailing environmental conditions. Remarkably, they possess the capability to modulate and influence various plant physiological processes, thereby inducing tolerance to both biotic and abiotic stresses. Furthermore, these exudates facilitate plant growth and aid in the remediation of environmental pollutants such as chemicals and heavy metals in agroecosystems. Much like live microbes, when applied, these exudates actively participate in the phyllosphere and rhizosphere, engaging in continuous interactions with plants and plant-associated microbes. Consequently, they play a pivotal role in reshaping the microbiome. The biostimulant properties exhibited by these exudates position them as promising biological components for fostering cleaner and more sustainable agricultural systems. Full article

(This article belongs to the Special Issue Plant Biostimulants—a Promising Tool in Organic Farming)

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20 pages, 846 KB

Open AccessEditor’s ChoiceReview

Indigo Carmine: Between Necessity and Concern

by Madalina-Elena Ristea and Otilia Zarnescu

J. Xenobiotics 2023, 13(3), 509-528; https://doi.org/10.3390/jox13030033 - 20 Sep 2023

Cited by 96 | Viewed by 15004

Abstract

Dyes, such as indigo carmine, have become indispensable to modern life, being widely used in the food, textile, pharmaceutical, medicine, and cosmetic industry. Although indigo carmine is considered toxic and has many adverse effects, it is found in many foods, and the maximum [...] Read more.

Dyes, such as indigo carmine, have become indispensable to modern life, being widely used in the food, textile, pharmaceutical, medicine, and cosmetic industry. Although indigo carmine is considered toxic and has many adverse effects, it is found in many foods, and the maximum permitted level is 500 mg/kg. Indigo carmine is one of the most used dyes in the textile industry, especially for dyeing denim, and it is also used in medicine due to its impressive applicability in diagnostic methods and surgical procedures, such as in gynecological and urological surgeries and microsurgery. It is reported that indigo carmine is toxic for humans and can cause various pathologies, such as hypertension, hypotension, skin irritations, or gastrointestinal disorders. In this review, we discuss the structure and properties of indigo carmine; its use in various industries and medicine; the adverse effects of its ingestion, injection, or skin contact; the effects on environmental pollution; and its toxicity testing. For this review, 147 studies were considered relevant. Most of the cited articles were those about environmental pollution with indigo carmine (51), uses of indigo carmine in medicine (45), and indigo carmine as a food additive (17). Full article

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22 pages, 1070 KB

Open AccessEditor’s ChoiceReview

Cytochrome P450 Gene Families: Role in Plant Secondary Metabolites Production and Plant Defense

by Panchali Chakraborty, Ashok Biswas, Susmita Dey, Tuli Bhattacharjee and Swapan Chakrabarty

J. Xenobiotics 2023, 13(3), 402-423; https://doi.org/10.3390/jox13030026 - 25 Jul 2023

Cited by 139 | Viewed by 16931

Abstract

Cytochrome P450s (CYPs) are the most prominent family of enzymes involved in NADPH- and O₂-dependent hydroxylation processes throughout all spheres of life. CYPs are crucial for the detoxification of xenobiotics in plants, insects, and other organisms. In addition to performing this [...] Read more.

Cytochrome P450s (CYPs) are the most prominent family of enzymes involved in NADPH- and O₂-dependent hydroxylation processes throughout all spheres of life. CYPs are crucial for the detoxification of xenobiotics in plants, insects, and other organisms. In addition to performing this function, CYPs serve as flexible catalysts and are essential for producing secondary metabolites, antioxidants, and phytohormones in higher plants. Numerous biotic and abiotic stresses frequently affect the growth and development of plants. They cause a dramatic decrease in crop yield and a deterioration in crop quality. Plants protect themselves against these stresses through different mechanisms, which are accomplished by the active participation of CYPs in several biosynthetic and detoxifying pathways. There are immense potentialities for using CYPs as a candidate for developing agricultural crop species resistant to biotic and abiotic stressors. This review provides an overview of the plant CYP families and their functions to plant secondary metabolite production and defense against different biotic and abiotic stresses. Full article

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19 pages, 769 KB

Open AccessEditor’s ChoiceSystematic Review

Systematic Review of Safety of Selective Androgen Receptor Modulators in Healthy Adults: Implications for Recreational Users

by Jonathan D. Vignali, Kevin C. Pak, Holly R. Beverley, Jesse P. DeLuca, John W. Downs, Adrian T. Kress, Brett W. Sadowski and Daniel J. Selig

J. Xenobiotics 2023, 13(2), 218-236; https://doi.org/10.3390/jox13020017 - 10 May 2023

Cited by 40 | Viewed by 35584

Abstract

Selective Androgen Receptor Modulators (SARMs) are not FDA approved, and obtaining SARMs for personal use is illegal. Nevertheless, SARM use is increasingly popular amongst recreational athletes. Recent case reports of drug-induced liver injury (DILI) and tendon rupture raise serious concerns for the safety [...] Read more.

Selective Androgen Receptor Modulators (SARMs) are not FDA approved, and obtaining SARMs for personal use is illegal. Nevertheless, SARM use is increasingly popular amongst recreational athletes. Recent case reports of drug-induced liver injury (DILI) and tendon rupture raise serious concerns for the safety of recreational SARM users. On 10 November 2022 PubMed, Scopus, Web of Science, and ClinicalTrials.gov were searched for studies that reported safety data of SARMs. A multi-tiered screening approach was utilized, and any study or case report of generally healthy individuals exposed to any SARM was included. Thirty-three studies were included in the review with 15 case reports or case series and 18 clinical trials (total patients N = 2136 patients, exposed to SARM N = 1447). There were case reports of drug-induced liver injury (DILI) (N = 15), Achilles tendon rupture (N = 1), rhabdomyolysis (N = 1), and mild reversible liver enzyme elevation (N = 1). Elevated alanine aminotransferase (ALT) was commonly reported in clinical trials in patients exposed to SARM (mean 7.1% across trials). Two individuals exposed to GSK2881078 in a clinical trial were reported to have rhabdomyolysis. Recreational SARM use should be strongly discouraged, and the risks of DILI, rhabdomyolysis, and tendon rupture should be emphasized. However, despite warnings, if a patient refuses to discontinue SARM use, ALT monitoring or dose reduction may improve early detection and prevention of DILI. Full article

(This article belongs to the Section Drug Therapeutics)

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21 pages, 1838 KB

Open AccessEditor’s ChoiceReview

Natural Products as a Tool to Modulate the Activity and Expression of Multidrug Resistance Proteins of Intestinal Barrier

by Carlos Martins-Gomes and Amélia M. Silva

J. Xenobiotics 2023, 13(2), 172-192; https://doi.org/10.3390/jox13020014 - 25 Mar 2023

Cited by 26 | Viewed by 8735

Abstract

The role of intestinal barrier homeostasis in an individual’s general well-being has been widely addressed by the scientific community. Colorectal cancer is among the illnesses that most affect this biological barrier. While chemotherapy is the first choice to treat this type of cancer, [...] Read more.

The role of intestinal barrier homeostasis in an individual’s general well-being has been widely addressed by the scientific community. Colorectal cancer is among the illnesses that most affect this biological barrier. While chemotherapy is the first choice to treat this type of cancer, multidrug resistance (MDR) is the major setback against the commonly used drugs, with the ATP-binding cassette transporters (ABC transporters) being the major players. The role of P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1), or breast cancer resistance protein (ABCG2) in the efflux of chemotherapeutic drugs is well described in cancer cells, highlighting these proteins as interesting druggable targets to reverse MDR, decrease drug dosage, and consequently undesired toxicity. Natural products, especially phytochemicals, have a wide diversity of chemical structures, and some particular classes, such as phenolic acids, flavonoids, or pentacyclic triterpenoids, have been reported as inhibitors of P-gp, MRP1, and ABCG2, being able to sensitize cancer cells to chemotherapy drugs. Nevertheless, ABC transporters play a vital role in the cell’s defense against xenobiotics, and some phytochemicals have also been shown to induce the transporters’ activity. A balance must be obtained between xenobiotic efflux in non-tumor cells and bioaccumulation of chemotherapy drugs in cancer cells, in which ABC transporters are essential and natural products play a pivotal role that must be further analyzed. This review summarizes the knowledge concerning the nomenclature and function of ABC-transporters, emphasizing their role in the intestinal barrier cells. In addition, it also focuses on the role of natural products commonly found in food products, e.g., phytochemicals, as modulators of ABC-transporter activity and expression, which are promising nutraceutical molecules to formulate new drug combinations to overcome multidrug resistance. Full article

(This article belongs to the Special Issue Journal of Xenobiotics: Feature Papers)

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15 pages, 462 KB

Open AccessEditor’s ChoiceArticle

Phytotherapy and Drugs: Can Their Interactions Increase Side Effects in Cancer Patients?

by Sarah Allegra, Silvia De Francia, Francesca Turco, Ilenia Bertaggia, Francesco Chiara, Tiziana Armando, Silvana Storto and Maria Valentina Mussa

J. Xenobiotics 2023, 13(1), 75-89; https://doi.org/10.3390/jox13010007 - 1 Feb 2023

Cited by 23 | Viewed by 10934

Abstract

Background: The use of herbs to treat illnesses was common in all historical eras. Our aim was to describe the phytotherapeutic substances that cancer patients use most commonly, and to determine whether their use can increase side effects. Methods: This was a retrospective [...] Read more.

Background: The use of herbs to treat illnesses was common in all historical eras. Our aim was to describe the phytotherapeutic substances that cancer patients use most commonly, and to determine whether their use can increase side effects. Methods: This was a retrospective and descriptive study conducted among older adults actively undergoing chemotherapy, admitted at the Oncology DH Unit (COES) of the Molinette Hospital AOU Città della Salute e della Scienza in Turin (Italy). Data collection was conducted through the distribution of self-compiled and closed-ended questionnaires during chemotherapy treatment. Results: A total of 281 patients were enrolled. Evaluating retching and sage consumption was statistically significant in multivariate analysis. The only risk factor for dysgeusia was chamomile consumption. Ginger, pomegranate, and vinegar use were retained as mucositis predictors. Conclusions: Phytotherapeutic use needs more attention in order to decrease the risks of side effects, toxicity, and ineffective treatment. The conscious administration of these substances should be promoted for safe use and to provide the reported benefits. Full article

(This article belongs to the Section Natural Products/Herbal Medicines)

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33 pages, 6178 KB

Open AccessEditor’s ChoiceArticle

Geospatiotemporal and Causal Inferential Study of European Epidemiological Patterns of Cannabis- and Substance-Related Congenital Orofacial Anomalies

by Albert Stuart Reece and Gary Kenneth Hulse

J. Xenobiotics 2023, 13(1), 42-74; https://doi.org/10.3390/jox13010006 - 1 Feb 2023

Cited by 7 | Viewed by 4923

Abstract

Introduction. Since high rates of congenital anomalies (CAs), including facial CAs (FCAs), causally attributed to antenatal and community cannabis use have been reported in several recent series, it was of interest to examine this subject in detail in Europe. Methods. CA data were [...] Read more.

Introduction. Since high rates of congenital anomalies (CAs), including facial CAs (FCAs), causally attributed to antenatal and community cannabis use have been reported in several recent series, it was of interest to examine this subject in detail in Europe. Methods. CA data were taken from the EUROCAT database. Drug exposure data were downloaded from the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). Income was taken from the World Bank’s online sources. Results. On the bivariate maps of both orofacial clefts and holoprosencephaly against resin, the Δ9-tetrahydrocannabinol concentration rates of both covariates increased together in France, Bulgaria, and the Netherlands. In the bivariate analysis, the anomalies could be ranked by the minimum E-value (mEV) as congenital glaucoma > congenital cataract > choanal atresia > cleft lip ± cleft palate > holoprosencephaly > orofacial clefts > ear, face, and neck anomalies. When nations with increasing daily use were compared to those without, the former had generally higher rates of FCAs (p = 0.0281). In the inverse probability weighted panel regression, the sequence of anomalies—orofacial clefts, anotia, congenital cataract, and holoprosencephaly—had positive and significant cannabis coefficients of p = 2.65 × 10⁻⁵, 1.04 × 10⁻⁸, 5.88 × 10⁻¹⁶, and 3.21 × 10⁻¹³, respectively. In the geospatial regression, the same series of FCAs had positive and significant regression terms for cannabis of p = 8.86 × 10⁻⁹, 0.0011, 3.36 × 10⁻⁸, and 0.0015, respectively. Some 25/28 (89.3%) E-value estimates and 14/28 (50%) mEVs were >9 (considered to be in the high range), and 100% of both were >1.25 (understood to be in the causal range). Conclusion. Rising cannabis use is associated with all the FCAs and fulfils the epidemiological criteria for causality. The data indicate particular concerns relating to brain development and exponential genotoxic dose-responses, urging caution with regard to community cannabinoid penetration. Full article

(This article belongs to the Section Natural Products/Herbal Medicines)

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