Journal of Xenobiotics

16 pages, 1860 KiB

Open AccessArticle

Associations between Non-Essential Trace Elements in Women’s Biofluids and IVF Outcomes in Euploid Single-Embryo Transfer Cycles

by Roberto Gonzalez-Martin, Andrea Palomar, Silvia Perez-Deben, Stefania Salsano, Alicia Quiñonero, Laura Caracena, Isabel Rucandio, Rocio Fernandez-Saavedra, Rodolfo Fernandez-Martinez, Estefania Conde-Vilda, Alberto J. Quejido, Juan Giles, Carmen Vidal, Jose Bellver and Francisco Dominguez

J. Xenobiot. 2024, 14(3), 1093-1108; https://doi.org/10.3390/jox14030062 (registering DOI) - 8 Aug 2024

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Abstract

Previous studies have found inconsistent associations between heavy metals and metalloids (cadmium, lead, mercury, and arsenic), and reproductive outcomes. The biofluid concentrations of ten non-essential trace elements (Hg, Pb, As, Ba, Sr, Rb, Cs, Sn, Ni, and Co) were evaluated in 51 Spanish [...] Read more.

Previous studies have found inconsistent associations between heavy metals and metalloids (cadmium, lead, mercury, and arsenic), and reproductive outcomes. The biofluid concentrations of ten non-essential trace elements (Hg, Pb, As, Ba, Sr, Rb, Cs, Sn, Ni, and Co) were evaluated in 51 Spanish women undergoing ICSI, PGT-A, and SET/FET. Nine out of ten non-essential elements were detectable in follicular fluid, whole blood, and urine collected the day of vaginal oocyte retrieval (VOR) and the day of embryo transfer and then analyzed by ICP-MS or Tricell DMA-80 for mercury. Elevated mercury and strontium concentrations in follicular fluid were associated with poor ovarian response and preimplantation outcomes. Worst preimplantation outcomes were also identified in women with elevated whole-blood strontium or mercury, urinary arsenic, barium, and tin the day of VOR. High concentrations of urinary rubidium on VOR day were linked with enhanced fertilization and blastocyst development. Excessive titanium in whole blood was associated with lower odds of implantation, clinical pregnancy, and achieving a live birth in a given IVF cycle. Excessive urinary arsenic on the day of embryo transfer was associated with lower odds of live birth. Although these preliminary results need to be confirmed in larger populations, distinguishing organic and inorganic element forms, our findings show that some non-essential elements have a detrimental impact on human IVF outcomes. Full article

(This article belongs to the Section Emerging Chemicals)

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14 pages, 3990 KiB

Open AccessArticle

Berberine Attenuates Acetamiprid Exposure-Induced Mitochondrial Dysfunction and Apoptosis in Rats via Regulating the Antioxidant Defense System

by Annu Phogat, Jagjeet Singh, Reena Sheoran, Arun Hasanpuri, Aakash Chaudhary, Shakti Bhardwaj, Sandeep Antil, Vijay Kumar, Chandra Prakash and Vinay Malik

J. Xenobiot. 2024, 14(3), 1079-1092; https://doi.org/10.3390/jox14030061 (registering DOI) - 7 Aug 2024

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Abstract

Acetamiprid (ACMP) is a neonicotinoid insecticide that poses a significant threat to the environment and mankind. Oxidative stress and mitochondrial dysfunction are considered prime contributors to ACMP-induced toxic effects. Meanwhile, berberine (BBR) a natural plant alkaloid, is a topic of interest because of [...] Read more.

Acetamiprid (ACMP) is a neonicotinoid insecticide that poses a significant threat to the environment and mankind. Oxidative stress and mitochondrial dysfunction are considered prime contributors to ACMP-induced toxic effects. Meanwhile, berberine (BBR) a natural plant alkaloid, is a topic of interest because of its therapeutic and prophylactic actions. Therefore, this study evaluated the effects of BBR on ACMP-mediated alterations in mitochondrial functions and apoptosis in rat liver tissue. Male Wistar rats were divided into four groups: (I) control, (II) BBR-treated, (III) ACMP-exposed, and (IV) BBR+ACMP co-treated groups. The doses of BBR (150 mg/kg b.wt) and ACMP (1/10 of LD_50, i.e., 21.7 mg/kg b.wt) were given intragastrically for 21 consecutive days. The results showed that the administration of ACMP diminished mitochondrial complex activity, downregulated complex I (ND1 and ND2) and complex IV (COX1 and COX4) subunit mRNA expression, depleted the antioxidant defense system, and induced apoptosis in rat liver. BBR pre-treatment significantly attenuated ACMP-induced mitochondrial dysfunction by maintaining mitochondrial complex activity and upregulating ND1, ND2, COX1, and COX4 mRNA expression. BBR reversed ACMP-mediated apoptosis by diminishing Bax and caspase-3 and increasing the Bcl-2 protein level. BBR also improved the mitochondrial antioxidant defense system by upregulating mRNA expression of PGC-1α, MnSOD, and UCP-2 in rat liver tissue. This study is the first to evaluate the protective potential of BBR against pesticide-induced mitochondrial dysfunction in liver tissue. In conclusion, BBR offers protection against ACMP-induced impairment in mitochondrial functions by maintaining the antioxidant level and modulating the apoptotic cascade. Full article

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15 pages, 3134 KiB

Open AccessArticle

Estrogenic Responsiveness of Brown Trout Primary Hepatocyte Spheroids to Environmental Levels of 17α-Ethinylestradiol

by Rodrigo F. Alves, Célia Lopes, Eduardo Rocha and Tânia Vieira Madureira

J. Xenobiot. 2024, 14(3), 1064-1078; https://doi.org/10.3390/jox14030060 (registering DOI) - 6 Aug 2024

Viewed by 218

Abstract

Three-dimensional (3D) fish hepatocyte cultures are promising alternative models for replicating in vivo data. Few studies have attempted to characterise the structure and function of fish 3D liver models and illustrate their applicability. This study aimed to further characterise a previously established spheroid [...] Read more.

Three-dimensional (3D) fish hepatocyte cultures are promising alternative models for replicating in vivo data. Few studies have attempted to characterise the structure and function of fish 3D liver models and illustrate their applicability. This study aimed to further characterise a previously established spheroid model obtained from juvenile brown trout (Salmo trutta) primary hepatocytes under estrogenic stimulation. The spheroids were exposed for six days to environmentally relevant concentrations of 17α-ethinylestradiol—EE2 (1–100 ng/L). The mRNA levels of peroxisome (catalase—Cat and urate oxidase—Uox), lipid metabolism (acyl-CoA long chain synthetase 1—Acsl1, apolipoprotein AI—ApoAI, and fatty acid binding protein 1—Fabp1), and estrogen-related (estrogen receptor α—ERα, estrogen receptor β—ERβ, vitellogenin A—VtgA, zona pellucida glycoprotein 2.5—ZP2.5, and zona pellucida glycoprotein 3a.2—ZP3a.2) target genes were evaluated by quantitative real-time polymerase chain reaction. Immunohistochemistry was used to assess Vtg and ZP protein expressions. At the highest EE2 concentration, VtgA and ZP2.5 genes were significantly upregulated. The remaining target genes were not significantly altered by EE2. Vtg and ZP immunostaining was consistently increased in spheroids exposed to 50 and 100 ng/L of EE2, whereas lower EE2 levels resulted in a weaker signal. EE2 did not induce significant changes in the spheroids’ viability and morphological parameters. This study identified EE2 effects at environmentally relevant doses in trout liver spheroids, indicating its usefulness as a proxy for in vivo impacts of xenoestrogens. Full article

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

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13 pages, 455 KiB

Open AccessArticle

Association between Liver and Kidney Function and Birth Outcomes in Pregnant Surinamese Women Exposed to Mercury and Lead in the Caribbean Consortium for Research in Environmental and Occupational Health (CCREOH) Environmental Epidemiologic Cohort Study

by Sheila Kort, Jeffrey Wickliffe, Arti Shankar, Hannah H. Covert, Maureen Lichtveld and Wilco Zijlmans

J. Xenobiot. 2024, 14(3), 1051-1063; https://doi.org/10.3390/jox14030059 - 1 Aug 2024

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Abstract

Exposure to mercury (Hg) and lead (Pb), in combination with liver and kidney impairment, may result in adverse birth outcomes. From 408 women in the age range of 16 to 46 years, living in rural and urban areas in the interior of Suriname, [...] Read more.

Exposure to mercury (Hg) and lead (Pb), in combination with liver and kidney impairment, may result in adverse birth outcomes. From 408 women in the age range of 16 to 46 years, living in rural and urban areas in the interior of Suriname, we looked at the association between adverse birth outcomes and exposure to Hg and Pb in combination with liver and kidney function. This group of women represented a subcohort of pregnant women who participated in the Caribbean Consortium for Research in Environmental and Occupational Health (CCREOH)—Meki Tamara study. Liver function was assessed by measuring aspartate amino transferase (AST), alanine amino transferase (ALT), and gamma-glutamyl transferase (GGT). Kidney function was assessed by measuring creatinine, urea, and cystatin C. We defined preterm births as birth before 37 weeks of gestation, low birthweight as birthweight < 2500 g, and low Apgar score as a score < 7 at 5 min, and these were used as indicators for adverse birth outcomes. Small size for gestational age was defined as gestational age < −2SD weight for GA. We found significant statistical associations between biomarkers for liver and kidney functions and adverse birth outcomes Apgar score and gestational age. No significant association was found between heavy metals Hg and lead and adverse birth outcomes. Full article

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

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15 pages, 2670 KiB

Open AccessArticle

Prenatal Exposure to Bisphenol A and/or Diethylhexyl Phthalate Impacts Brain Monoamine Levels in Rat Offspring

by Amrita Kaimal, Jessica M. Hooversmith, Maryam H. Al Mansi, Philip V. Holmes, Puliyur S. MohanKumar and Sheba M. J. MohanKumar

J. Xenobiot. 2024, 14(3), 1036-1050; https://doi.org/10.3390/jox14030058 - 1 Aug 2024

Viewed by 327

Abstract

This study examines the sex-specific effects of gestational exposure (days 6–21) to endocrine-disrupting chemicals such as bisphenol A (BPA), diethylhexyl phthalate (DEHP), or their combination on brain monoamine levels that play an important role in regulating behavior. Pregnant Sprague–Dawley rats were orally administered [...] Read more.

This study examines the sex-specific effects of gestational exposure (days 6–21) to endocrine-disrupting chemicals such as bisphenol A (BPA), diethylhexyl phthalate (DEHP), or their combination on brain monoamine levels that play an important role in regulating behavior. Pregnant Sprague–Dawley rats were orally administered saline, low doses (5 µg/kg BW/day) of BPA or DEHP, and their combination or a high dose (7.5 mg/kg BW/day) of DEHP alone or in combination with BPA during pregnancy. The offspring were subjected to a behavioral test and sacrificed in adulthood, and the brains were analyzed for neurotransmitter levels. In the paraventricular nucleus, there was a marked reduction in dopamine levels (p < 0.01) in male offspring from the BPA, DEHP, and B + D (HD) groups, which correlated well with their shock probe defensive burying times. Neurotransmitter changes in all brain regions examined were significant in female offspring, with DEHP (HD) females being affected the most, followed by the B + D groups. BPA and/or DEHP (LD) increased monoamine turnover in a region-specific manner in male offspring (p < 0.05). Overall, prenatal exposure to BPA, DEHP, or their combination alters monoamine levels in a brain region-specific, sex-specific, and dose-dependent manner, which could have implications for their behavioral and neuroendocrine effects. Full article

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

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13 pages, 3020 KiB

Open AccessArticle

Incorporating Tissue-Specific Gene Expression Data to Improve Chemical–Disease Inference of in Silico Toxicogenomics Methods

by Shan-Shan Wang, Chia-Chi Wang, Chien-Lun Wang, Ying-Chi Lin and Chun-Wei Tung

J. Xenobiot. 2024, 14(3), 1023-1035; https://doi.org/10.3390/jox14030057 - 31 Jul 2024

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Abstract

In silico toxicogenomics methods are resource- and time-efficient approaches for inferring chemical–protein–disease associations with potential mechanism information for exploring toxicological effects. However, current in silico toxicogenomics systems make inferences based on only chemical–protein interactions without considering tissue-specific gene/protein expressions. As a result, inferred [...] Read more.

In silico toxicogenomics methods are resource- and time-efficient approaches for inferring chemical–protein–disease associations with potential mechanism information for exploring toxicological effects. However, current in silico toxicogenomics systems make inferences based on only chemical–protein interactions without considering tissue-specific gene/protein expressions. As a result, inferred diseases could be overpredicted with false positives. In this work, six tissue-specific expression datasets of genes and proteins were collected from the Expression Atlas. Genes were then categorized into high, medium, and low expression levels in a tissue- and dataset-specific manner. Subsequently, the tissue-specific expression datasets were incorporated into the chemical–protein–disease inference process of our ChemDIS system by filtering out relatively low-expressed genes. By incorporating tissue-specific gene/protein expression data, the enrichment rate for chemical–disease inference was largely improved with up to 62.26% improvement. A case study of melamine showed the ability of the proposed method to identify more specific disease terms that are consistent with the literature. A user-friendly user interface was implemented in the ChemDIS system. The methodology is expected to be useful for chemical–disease inference and can be implemented for other in silico toxicogenomics tools. Full article

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20 pages, 109182 KiB

Open AccessArticle

In Vivo Antischistosomicidal and Immunomodulatory Effects of Dietary Supplementation with Taraxacum officinale

by Amany Ebrahim Nofal, Amal Mohamed Shaaban, Hany Mohammed Ibrahim, Faten Abouelmagd and Azza Hassan Mohamed

J. Xenobiot. 2024, 14(3), 1003-1022; https://doi.org/10.3390/jox14030056 - 29 Jul 2024

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Abstract

Bilharziasis is a widespread trematode parasite that poses a severe public health burden. Dandelion (Taraxacum officinale) has several pharmacological and traditional properties critical for treating several hepatic disorders. The present study was designed to assess the potential efficacy of T. officinale [...] Read more.

Bilharziasis is a widespread trematode parasite that poses a severe public health burden. Dandelion (Taraxacum officinale) has several pharmacological and traditional properties critical for treating several hepatic disorders. The present study was designed to assess the potential efficacy of T. officinale root (TOR) dietary supplementation with or without praziquantel (PZQ) against liver and intestinal disorders in mice infected with Schistosoma mansoni. This study was conducted on five groups; G1: uninfected control, G2: untreated S. mansoni-infected mice, G3: infected animals treated with 250 mg/kg PZQ for three alternative days, G4: infected animals were orally administered 600 mg/kg bw TOR daily for 10 days, and G5: infected animals that received both PZQ and TOR as previously described. The current findings after different treatments indicated topographical scanning electron microscopy alterations of male adult worms and a critical reduction in worm burden, ova count, granuloma diameter, hepatic and intestinal histological abnormalities, fibrosis, immunohistochemical expression of CD3⁺ and CD20⁺ cells, oxidative stress, and interleukin-10, also upregulation of interferon-gamma, and antioxidant enzymes, when compared to the infected untreated mice. The best results were obtained in mice administered PZQ+TOR together because of their antioxidant properties and ability to promote the host immune response to parasitic infection. Full article

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

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14 pages, 3334 KiB

Open AccessArticle

Pollution of Beach Sands of the Ob River (Western Siberia) with Microplastics and Persistent Organic Pollutants

by Yulia A. Frank, Yulia S. Sotnikova, Vasiliy Yu. Tsygankov, Aleksey R. Rednikin, Maksim M. Donets, Elena V. Karpova, Maksim A. Belanov, Svetlana Rakhmatullina, Aleksandra D. Borovkova, Dmitriy N. Polovyanenko and Danil S. Vorobiev

J. Xenobiot. 2024, 14(3), 989-1002; https://doi.org/10.3390/jox14030055 - 25 Jul 2024

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Abstract

Microplastics (MPs) in aquatic environments can be associated with various substances, including persistent organic pollutants, which add to the problem of plastic ecotoxicity. The abundance of 1–5 mm microplastics and concentrations of particle-adsorbed organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in sandy sediments [...] Read more.

Microplastics (MPs) in aquatic environments can be associated with various substances, including persistent organic pollutants, which add to the problem of plastic ecotoxicity. The abundance of 1–5 mm microplastics and concentrations of particle-adsorbed organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in sandy sediments from three beaches in recreational areas along the upper Ob River in Western Siberia were assessed. MP pollution levels in the Ob River beach sands ranged from 24 ± 20.7 to 104 ± 46.2 items m⁻² or, in terms of mass concentration, from 0.26 ± 0.21 to 1.22 ± 0.39 mg m⁻². The average abundance of MP particles reached 0.67 ± 0.58 items kg⁻¹ or 8.22 ± 6.13 μg kg⁻¹ in the studied sediments. MP concentrations were significantly higher in number (p < 0.05) and mass (p < 0.01) at the riverbank site downstream of the Novosibirsk wastewater treatment plant (WWTP) outfall compared to these at the upstream and more distant beaches. Most MPs (70–100%) were represented by irregularly shaped fragments. The polymer composition of MPs varied between sites, with a general predominance of polyethylene (PE). The study revealed associations of MPs with PCBs and OCPs not previously detected in the riverbed and beach sediments, suggesting that these substances are circulating in the Ob River basin. Although MP concentrations were higher downstream of the WWTP, the maximum levels of particle-associated OCPs were observed in the beach sands of the site farthest from the urban agglomeration. The pesticides γ-HCH, 4,4-DDT, and 4,4-DDE were detected on MPs at relatively low concentrations. PCBs were more abundant in the studied samples, including 118 dioxin-like congener. The results obtained indicate that the Ob River is susceptible to plastic and persistent organic pollutant (POP) contamination and serve as a starting point for further studies and practical solutions to the problem. Full article

(This article belongs to the Section Emerging Chemicals)

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19 pages, 6798 KiB

Open AccessArticle

The Impact of Metolachlor Applications and Phytoremediation Processes on Soil Microorganisms: Insights from Functional Metagenomics Analysis

by Seyedeh Parvin Hejazirad, Caique Menezes de Abreu, Guilherme Henrique Fernandes Carneiro, Carlos Rodrigues Gomes, Paulo Roberto de Carvalho Spinola Filho, Márcia Regina da Costa and José Barbosa dos Santos

J. Xenobiot. 2024, 14(3), 970-988; https://doi.org/10.3390/jox14030054 - 23 Jul 2024

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Abstract

This study assessed the impact of phytoremediation on reducing the residual concentration of metolachlor in soil treated with doses of 530.7 and 1061.4 g/ha and its effect on microbial biodiversity in contaminated areas. For the plant species Avena sativa and Medicago sativa, [...] Read more.

This study assessed the impact of phytoremediation on reducing the residual concentration of metolachlor in soil treated with doses of 530.7 and 1061.4 g/ha and its effect on microbial biodiversity in contaminated areas. For the plant species Avena sativa and Medicago sativa, a significant efficacy of 54.5 and 36.4% was observed in the dissipation of the herbicide, especially at higher doses. Although metolachlor application reduced soil microbial biodiversity, phytoremediating plants, especially M. sativa, promoted greater richness and distribution of microbial species, mitigating the negative effects of the herbicide. Principal component analysis revealed the influence of these plants and metolachlor on the composition of the microbial community. These results highlight the importance of phytoremediation in promoting soil biodiversity and reducing herbicide contamination, providing crucial insights for remediation strategies in contaminated areas. Full article

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

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20 pages, 7856 KiB

Open AccessArticle

Chronic Exposure to Both Electronic and Conventional Cigarettes Alters Ileum and Colon Turnover, Immune Function, and Barrier Integrity in Mice

by Madjid Djouina, Anaïs Ollivier, Christophe Waxin, Gwenola Kervoaze, Muriel Pichavant, Ségolène Caboche, Djamal Achour, Céline Grare, Delphine Beury, David Hot, Sébastien Anthérieu, Jean-Marc Lo-Guidice, Laurent Dubuquoy, David Launay, Cécile Vignal, Philippe Gosset and Mathilde Body-Malapel

J. Xenobiot. 2024, 14(3), 950-969; https://doi.org/10.3390/jox14030053 - 22 Jul 2024

Viewed by 501

Abstract

Although the effects of cigarette smoke (CS) on the development of several intestinal diseases is well documented, the impact of e-cigarette aerosol (e-cig) on digestive health is largely unknown. To compare the effects of e-cig and CS on mouse ileum and colon, animals [...] Read more.

Although the effects of cigarette smoke (CS) on the development of several intestinal diseases is well documented, the impact of e-cigarette aerosol (e-cig) on digestive health is largely unknown. To compare the effects of e-cig and CS on mouse ileum and colon, animals were chronically exposed for 6 months by nose-only inhalation to e-cig at 18 or 30 W power, or to 3R4F CS. Results showed that e-cig exposure decreased colon cell proliferation. Several other proliferative defects were observed in response to both e-cig and CS exposure, including up- and down-regulation of cyclin D1 protein levels in the ileum and colon, respectively. E-cig and CS exposure reduced myeloperoxidase activity in the ileum. In the colon, both exposures disrupted gene expression of cytokines and T cell transcription factors. For tight junction genes, ZO-1- and occludin-protein expression levels were reduced in the ileum and colon, respectively, by e-cig and CS exposure. The 16S sequencing of microbiota showed specific mild dysbiosis, according to the type of exposure. Overall, e-cig exposure led to altered proliferation, inflammation, and barrier function in both the ileum and colon, and therefore may be a gut hazard on par with conventional CS. Full article

(This article belongs to the Topic Toxins in Medical Toxicology)

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11 pages, 2406 KiB

Open AccessCommunication

Underexplored Molecular Mechanisms of Toxicity

by Olatunbosun Arowolo and Alexander Suvorov

J. Xenobiot. 2024, 14(3), 939-949; https://doi.org/10.3390/jox14030052 - 18 Jul 2024

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Abstract

Social biases may concentrate the attention of researchers on a small number of well-known molecules/mechanisms leaving others underexplored. In accordance with this view, central to mechanistic toxicology is a narrow range of molecular pathways that are assumed to be involved in a significant [...] Read more.

Social biases may concentrate the attention of researchers on a small number of well-known molecules/mechanisms leaving others underexplored. In accordance with this view, central to mechanistic toxicology is a narrow range of molecular pathways that are assumed to be involved in a significant part of the responses to toxicity. It is unclear, however, if there are other molecular mechanisms which play an important role in toxicity events but are overlooked by toxicology. To identify overlooked genes sensitive to chemical exposures, we used publicly available databases. First, we used data on the published chemical–gene interactions for 17,338 genes to estimate their sensitivity to chemical exposures. Next, we extracted data on publication numbers per gene for 19,243 human genes from the Find My Understudied Genes database. Thresholds were applied to both datasets using our algorithm to identify chemically sensitive and chemically insensitive genes and well-studied and underexplored genes. A total of 1110 underexplored genes highly sensitive to chemical exposures were used in GSEA and Shiny GO analyses to identify enriched biological categories. The metabolism of fatty acids, amino acids, and glucose were identified as underexplored molecular mechanisms sensitive to chemical exposures. These findings suggest that future effort is needed to uncover the role of xenobiotics in the current epidemics of metabolic diseases. Full article

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16 pages, 6113 KiB

Open AccessArticle

Toxic Effects of Carbaryl Exposure on Juvenile Asian Seabass (Lates calcarifer)

by Junhua Huang, Zhengyi Fu, Wei Yu, Zemin Bai and Zhenhua Ma

J. Xenobiot. 2024, 14(3), 923-938; https://doi.org/10.3390/jox14030051 - 10 Jul 2024

Viewed by 481

Abstract

This study examines the physiological and immunological effects of 0.5 ppm carbaryl exposure on juvenile Asian seabass (Lates calcarifer) over 12 h to 72 h. Notable results include decreased activities of liver enzymes catalase (CAT), lactate dehydrogenase (LDH), and glutathione peroxidase [...] Read more.

This study examines the physiological and immunological effects of 0.5 ppm carbaryl exposure on juvenile Asian seabass (Lates calcarifer) over 12 h to 72 h. Notable results include decreased activities of liver enzymes catalase (CAT), lactate dehydrogenase (LDH), and glutathione peroxidase (GSH-PX), while superoxide dismutase (SOD) levels remained stable, with the lowest activities of CAT and GSH-PX observed at 72 h. Serum biochemistry revealed increased alkaline phosphatase (AKP) and acid phosphatase (ACP) at 24 h, with declining aspartate aminotransferase (AST) and a peak in creatinine at 48 h. Histopathological analysis showed carbaryl-induced necrosis in liver and spleen cells, and increased melanomacrophage centers in both organs. Additionally, immune gene expression analysis indicated an upregulation of heat shock proteins and consistent elevation of complement component C3 and interleukin-8 (IL-8). These findings suggest that carbaryl exposure significantly impairs organ function and modulates immune responses in L. calcarifer, underlining the need for further research on protective strategies against pesticide impacts in aquaculture. Full article

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16 pages, 1782 KiB

Open AccessArticle

Ionic Liquid 1-Octyl-3-Methylimidazolium (M8OI) Is Mono-Oxygenated by CYP3A4 and CYP3A5 in Adult Human Liver

by Alistair C. Leitch, Tarek M. Abdelghany, Alex Charlton, Martin Cooke and Matthew C. Wright

J. Xenobiot. 2024, 14(3), 907-922; https://doi.org/10.3390/jox14030050 - 9 Jul 2024

Cited by 1 | Viewed by 584

Abstract

Environmental sampling around a landfill site in the UK previously identified the methylimidazolium ionic liquid, 1-octyl-3-methylimidazolium (M8OI), in the soil. More recently, M8OI was shown to be detectable in sera from 5/20 PBC patients and 1/10 controls and to be oxidised on the [...] Read more.

Environmental sampling around a landfill site in the UK previously identified the methylimidazolium ionic liquid, 1-octyl-3-methylimidazolium (M8OI), in the soil. More recently, M8OI was shown to be detectable in sera from 5/20 PBC patients and 1/10 controls and to be oxidised on the alkyl chain in the human liver. The objective of this study was to examine the metabolism of M8OI in humans in more detail. In human hepatocytes, M8OI was mono-oxygenated to 1-(8-Hydroxyoctyl)-3-methyl-imidazolium (HO8IM) then further oxidised to 1-(7-carboxyheptyl)-3-methyl-1H-imidazol-3-ium (COOH7IM). The addition of ketoconazole—in contrast to a range of other cytochrome P450 inhibitors—blocked M8OI metabolism, suggesting primarily CYP3A-dependent mono-oxygenation of M8OI. Hepatocytes from one donor produced negligible and low levels of HO8IM and COOH7IM, respectively, on incubation with M8OI, when compared to hepatocytes from other donors. This donor had undetectable levels of CYP3A4 protein and low CYP3A enzyme activity. Transcript expression levels for other adult CYP3A isoforms—CYP3A5 and CYP3A43—suggest that a lack of CYP3A4 accounted primarily for this donor’s low rate of M8OI oxidation. Insect cell (supersome) expression of various human CYPs identified CYP3A4 as the most active CYP mediating M8OI mono-oxygenation, followed by CYP3A5. HO8IM and COOH7IM were not toxic to human hepatocytes, in contrast to M8OI, and using a pooled preparation of human hepatocytes from five donors, ketoconazole potentiated M8OI toxicity. These data demonstrate that CYP3A initiates the mono-oxygenation and detoxification of M8OI in adult human livers and that CYP3A4 likely plays a major role in this process. Full article

(This article belongs to the Section Emerging Chemicals)

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14 pages, 1790 KiB

Open AccessArticle

Contamination Profiles of Selected Pollutants in Procambarus clarkii Non-Edible Portions Highlight Their Potential Exploitation Applications

by Dario Savoca, Mirella Vazzana, Vincenzo Arizza, Antonella Maccotta, Santino Orecchio, Francesco Longo, Vittoria Giudice, Gaetano D’Oca, Salvatore Messina, Federico Marrone and Manuela Mauro

J. Xenobiot. 2024, 14(3), 893-906; https://doi.org/10.3390/jox14030049 - 6 Jul 2024

Viewed by 645

Abstract

Properly managing aquatic organisms is crucial, including protecting endemic species and controlling invasive species. From a circular economy perspective, the sustainable use of aquatic species as a source of bioactive molecules is an area that is increasingly being explored. This includes the use [...] Read more.

Properly managing aquatic organisms is crucial, including protecting endemic species and controlling invasive species. From a circular economy perspective, the sustainable use of aquatic species as a source of bioactive molecules is an area that is increasingly being explored. This includes the use of non-edible portions of seafood, which could pose considerable risks to the environment due to current methods of disposal. Therefore, it is of paramount importance to ensure that the exploitation of these resources does not result in the transfer of pollutants to the final product. This study analyzed two types of non-edible parts from the crayfish Procambarus clarkii: the abdominal portion of the exoskeleton (AbE) and the whole exoskeleton (WE), including the cephalothorax. These portions could potentially be utilized in the context of eradication activities regulated by local authorities. A screening analysis of four classes of pollutants, including pesticides, per- and polyfluoroalkyl substances (PFAS), phthalic acid esters (PAEs), and trace elements (TEs), was performed. The only analytes detected were TEs, and significant differences in the contamination profile were found between AbE and WE. Nevertheless, the levels recorded were comparable to or lower than those reported in the literature and below the maximum levels allowed in the current European legislation for food, suggesting that their potential use is legally permitted. In terms of scalability, the utilization of the entire non-edible P. clarkii portion would represent a sustainable solution for the reuse of waste products. Full article

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20 pages, 1319 KiB

Open AccessArticle

Temporal Analysis of Pharmaceuticals as Emerging Contaminants in Surface Water and Wastewater Samples: A Case Study

by Paula Paíga, Luísa Correia-Sá, Manuela Correia, Sónia Figueiredo, Joana Vieira, Sandra Jorge, Jaime Gabriel Silva and Cristina Delerue-Matos

J. Xenobiot. 2024, 14(3), 873-892; https://doi.org/10.3390/jox14030048 - 3 Jul 2024

Viewed by 869

Abstract

Pharmaceuticals in the environment are a global concern, with studies in all continents highlighting their widespread occurrence and potential ecological impacts, revealing their presence, fate, and associated risks in aquatic ecosystems. Despite typically occurring at low concentrations (ranging from ng/L to µg/L), advancements [...] Read more.

Pharmaceuticals in the environment are a global concern, with studies in all continents highlighting their widespread occurrence and potential ecological impacts, revealing their presence, fate, and associated risks in aquatic ecosystems. Despite typically occurring at low concentrations (ranging from ng/L to µg/L), advancements in analytical methods and more sensitive equipment have enabled the detection of a higher number of pharmaceuticals. In this study, surface and wastewater samples were extracted using solid phase extraction and analyzed using ultra-high-performance liquid chromatography with tandem mass spectrometry. Among the therapeutic classes investigated, nonsteroidal anti-inflammatory drugs/analgesics, antibiotics, and psychiatric drugs showed a higher number of detected pharmaceuticals. Concentrations ranged from below method detection limit (<MDL) to 3.20 µg/L (caffeine) and <MDL to 639 µg/L (hydroxyibuprofen) in 2018, and from <MDL to 0.848 µg/L (diclofenac) and <MDL to 53.0 µg/L (caffeine) in 2019 for river water and wastewater samples. Temporal analysis showed an increase in the sum of pharmaceutical concentrations over the study years, highlighting the importance of monitoring pharmaceuticals in the environment and their potential accumulation over time. Full article

(This article belongs to the Special Issue Pharmaceuticals and Personal Care Products: From Exposure to Impacts on Human, Animal and Ecosystem Health towards an Integrated One Health Approach)

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46 pages, 5926 KiB

Open AccessReview

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

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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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J. Xenobiot., Volume 14, Issue 3 (September 2024) – 16 articles

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