Search Results (362)

Selenium (Se) is an essential trace element required for various physiological functions in agriculture. Nanotechnology is applied to produce selenium nanoparticles (SeNPs) that offer new advantages, enhancing their bioavailability and reducing toxicity. To further improve the stability of Se nanoelements in the poultry industry, the grey form of Se was recently offered as a potential alternative. However, its impact on bioaccessibility, metabolism, and overall animal efficiency remains undetermined. This study investigates the impact of red and grey SeNPs on Se content in the liver, blood cellular fraction (BCF), kidney, testis, and eyes, as well as the feed intake (FI) and growth performance, of adult Japanese quails. Adult quails were randomly assigned to five groups: a control (C0) and four groups receiving either red or grey Se nanoparticles (SeNPs) at 0.05 or 0.5 mg/kg, in addition to the basal diet which already contained 0.042 mg/kg Se from the premix, resulting in total Se contents of approximately 0.092 and 0.542 mg/kg in the treatment groups (T1–T4), with four replicates per group. The growth performance of quails fed with nano-Se-supplemented diets showed significant variation across groups (p < 0.05), with body weight differing by up to 20% between the highest performing group (T2) and the lowest (T1). FI showed no significant differences across groups. The results indicated that Se accumulation differed significantly between treatments. The selenium levels in the liver increased in a dose-dependent manner, with the highest accumulation observed in T4 (0.5 mg/kg grey SeNPs), at 42% above control levels. This pattern suggests that the liver is a primary organ for selenium storage and metabolism. The greatest Se content in BCFs was recorded in the groups that received grey selenium (T3 and T4) and red selenium at high concentrations (T2), while the group given red selenium at low concentrations (T1) and the control (C0) had the lowest Se accumulation. In the kidney tissues and testis, the Se content exhibited no significant differences between the treated groups and the control. The observed variations in the eye and breast muscle Se content among treatment groups reflect the differences in selenium bioavailability, metabolism, and tissue-specific regulatory mechanisms. These findings demonstrate that grey SeNPs can significantly elevate Se bioavailability in quails, particularly in target organs, and enhance the growth performance without notable changes in feed intake. This highlights the potential of SeNPs in enhancing quail nutrition, although further research is needed to establish optimal dosing strategies for safe, effective use. Full article

Municipal Solid Waste Incinerators (MSWIs) are facilities designed to burn municipal solid waste to reduce its volume and mass and generate energy. A significant concern related to MSWIs is the emission of toxic and carcinogenic pollutants, including polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs), heavy metals, and particulate matter. This review synthesizes global epidemiological and exposure assessment studies investigating cancer risks associated with residential proximity to MSWIs. Findings reveal a complex relationship: older incinerators with high emissions correlate with elevated risks of non-Hodgkin lymphoma (NHL), soft-tissue sarcoma (STS), and liver cancer in some studies, particularly in Europe. However, results remain inconsistent due to methodological limitations such as exposure misclassification, latency periods, and confounding factors like socioeconomic status. Modern facilities equipped with advanced pollution control technologies demonstrate reduced risks, often within regulatory thresholds. Key challenges include accurately quantifying historical exposures and disentangling MSWI-specific risks from other environmental or lifestyle factors. While advancements in dispersion modeling and biomonitoring have improved risk assessments, geographical and temporal variations in findings underscore the need for continued research. The review concludes that while historical evidence suggests potential cancer risks near older MSWIs, stricter emissions regulations and technological improvements have mitigated health impacts, although vigilance through long-term monitoring remains essential to safeguard public health. Full article

While meat consumption trends show decreases in some high-income countries, significant increases are observed elsewhere. Although this includes African nations, the average meat consumption in Africa remains generally lower than in many other continents, though patterns vary regionally. Meat provides essential nutrients, but inadequate consumption can pose health problems, while consumption also carries risks including potential exposure to environmental contaminants. This comprehensive review focuses on the recent scientific literature (published 2000–2024) regarding human exposure to specific toxic trace elements, namely arsenic (As), cadmium (Cd), mercury (Hg), lead (Pb), chromium (Cr, particularly hexavalent chromium, Cr(VI)), and nickel (Ni), through the consumption of meat (muscle tissues, organs, and processed products) in Africa. Limited data exist for many African regions, with most studies from Nigeria. Concentrations of these toxic elements in meat tissues varied significantly, with organs like liver and kidney showing higher levels than muscle tissues. Estimated dietary intakes also varied, with some studies indicating potential health risks from Pb, Cd, and As exceeding safety guidelines in specific contexts. However, meat is generally not the primary dietary source of these elements compared to fish, seafood, or staple crops, though risks are higher in areas near pollution sources like mines or waste sites. This study highlights the need for broader research across Central and North Africa, stricter monitoring of meat from high-risk areas, and standardized methodologies to protect public health. Full article

Background/Objectives: Liver-on-a-chip (LiOC) technology is increasingly recognized as a transformative platform for modeling liver biology, disease mechanisms, drug metabolism, and toxicity screening. Traditional two-dimensional (2D) in vitro models lack the complexity needed to replicate the liver’s unique microenvironment. This review aims to summarize recent advancements in LiOC systems, emphasizing their potential in biomedical research and translational applications. Methods: This narrative review synthesizes findings from key studies on the development and application of LiOC platforms. We explored innovations in material science and bioengineering, including microfluidic design, 3D printing, stem cell– and tissue-derived liver organoid integration, and co-culture strategies. Commercially available LiOC systems and their regulatory relevance were also evaluated. Results: LiOC systems have evolved from simple PDMS-based chips to complex, multicellular constructs incorporating hepatocytes, endothelial cells, Kupffer cells, and hepatic stellate cells. Recent studies demonstrate their superior ability to replicate liver-specific architecture and functions. Applications span cancer research, drug toxicity assessment (e.g., drug-induced liver injury prediction with >85% sensitivity), disease modeling, and regenerative medicine. Several platforms have gained FDA recognition and are in active use for preclinical drug testing. Conclusions: LiOC technology offers a more physiologically relevant alternative to traditional models and holds promise for reducing reliance on animal studies. While challenges remain, such as vascularization and long-term function, ongoing advancements are paving the way toward clinical and pharmaceutical integration. The technology is poised to play a key role in personalized medicine and next-generation therapeutic development. Full article

Metformin is the preferred first-line treatment for non-insulin-dependent diabetes mellitus, known for its benefits in cancer suppression, weight loss, and antiketogenic activity. It is a leading drug regarding mass distribution, and its high solubility in water leads to its significant accumulation in surface and groundwater. While some studies have explored its degradation products and toxicological consequences, none have specifically examined the impact of individual natural minerals and their mechanisms leading to these degraded compounds. Our investigation focuses on understanding the mineralogical effects of different photocatalysts and organic matter while assessing acute toxicity through cell viability tests on human cell lines. We utilized a custom-built reactor system containing metformin hydrochloride, photocatalysts, and organic matter under oxidizing conditions to explore the formation of new degraded compounds. We assessed the acute toxicity of both metformin hydrochloride and the resulting chemical mixture on kidney and liver cell lines using the colorimetric MTT cell viability assay. Despite the abundance of surface functional groups in organic humic acid, only solar energy-driven catalysts were found to effectively break down this widely used medication. Comparative analysis of metformin hydrochloride and its degraded residues indicates a toxic effect on liver cells. Our experiments contribute to understanding the environmental fate of metformin and pave the way for further biochemical investigations to identify toxicological mechanisms. Full article

Ustilaginoidin D is a type of bis-naphtho-γ-pyrone mycotoxin produced by Ustilaginoidea virens, the causal agent of rice false smut. Although previous studies have demonstrated the inhibitory effect of ustilaginoidin D on ATP synthesis and cancer cell growth in mice, its specific health risks remain unclear. Here, we reveal that ustilaginoidin D is highly toxic to mice with an LD₅₀ value of 213 mg /kg·bw. Dose-dependent weight loss and liver damage were observed, accompanied by altered markers of liver cell damage, including the enzyme activities of alanine aminotransferase and aspartate aminotransferase and the content of glutathione in mouse liver. RNA-seq analysis of liver tissues from mice treated with 150 mg of ustilaginoidin D/kg·bw identified significant changes in gene expression profiles, with differentially expressed genes enriched in cancer-related pathways, hypertrophic cardiomyopathy, and metabolic pathways. RT-qPCR data are highly consistent with transcriptome analysis in expression profiles of 22 chemical-carcinogenesis-associated genes. These findings indicate that ustilaginoidin D induces acute toxicity and liver dysfunction in mice, raising serious concerns about its threat to human health. Full article

Wheat bran, rich in phenolic compounds like ferulic acid, possesses notable antioxidant properties that may contribute to cancer treatment strategies. This study examined the effects of hydrolyzed arabinoxylan oligomers (HAOs) linked with ferulic acid from hard wheat bran on three human cancer cell lines: colon cancer (SW480), liver cancer (HepG2), and cervical cancer (HeLa). Cells were cultured in a three-dimensional (3D) 0.5% PGS matrix and exposed to varying concentrations (100, 500, and 1000 μg/mL) of wheat bran antioxidants (WBA) extracts. Results show that WBA inhibited growth of SW480 cells, significantly reducing spheroid expansion and promoting dehydration. In contrast, HepG2 cells exhibited increased growth under WBA treatment, suggesting a non-toxic, growth-enhancing effect. No significant changes were observed in HeLa cell growth, with cell viability remaining high across all treatments. These findings highlight the selective influence of WBA on cancer cell behavior, underscoring its potential for targeted, personalized cancer therapies. This study provides valuable insights into the application of antioxidant-rich compounds for modulating specific cancer cell dynamics, paving the way for novel therapeutic approaches. Full article

The term “plastics” is an umbrella term generally referring to any material containing a high level of polymer content as an essential ingredient. Micro(nano)plastics (MNPs) are derived from the degradation of plastics, representing exogenous substances whose exposure can potentially interfere with different physiological processes. In this scenario, even considering the relative paramount detoxification role, the liver emerges as a key active organ in the relationship between plastic exposure and human disease. In industrialized countries, where plastics constitute largely diffused components of objects routinely adopted in daily/social life, including food packaging, Metabolic dysfunction-associated Steatotic Liver Disease (MASLD) represents the predominant hepatopathy and is progressively becoming the leading cause of cirrhosis and liver cancer, with an incompletely elucidated multifactorial pathogenesis. Notably, oral exposure to MNPs has been revealed to impact the gut–liver axis by influencing gut microbiota composition, gastrointestinal absorption, and, ultimately, determining hepatic accumulation. At the hepatic level, MNPs can contribute to the onset and worsening of steatosis by inducing metabolic dysfunction and inflammation. Plastics can also serve as vectors for different potentially toxic additives, with specific MNPs constituting a persistent source of release of bisphenol A (BPA), a well-recognized exogenous etiological factor contributing to MASLD genesis and worsening. Recently, exposure to MNPs and additives has demonstrated significant impacts on the immune system, oxidative stress, and metabolism. In particular, polystyrene-derived MNPs impair the mechanisms regulating hepatic lipid metabolism, simultaneously acting as antigens abnormally triggering the innate immune response. At the same time, environmental BPA exposure has been revealed to trigger trained immunity-related pathways, configuring novel pathogenetic drivers potentially promoting the progression of MASLD. The present review, after rapidly overviewing the main sources and toxicological properties of MNPs and related additives, explores plastic-related exposure’s potential implications in the genesis and progression of hepatic steatosis, highlighting the urgent need for further clarification of relative pathogenetic mechanisms. Full article

Background: Photodynamic therapy (PDT) utilizing nano-based photosensitizers (PSs) offers promising cancer treatment potential but requires rigorous safety evaluation. Conjugated polymer nanoparticles (CPNs) doped with porphyrins, such as platinum porphyrin–doped poly(9,9-dioctylfluorene-alt-benzothiadiazole) (F8BT), exhibit enhanced photodynamic efficiency but lack comprehensive preclinical toxicity data. This study aimed to evaluate the biocompatibility, biodistribution, and acute/subacute toxicity of these CPNs to establish their safety profile for clinical translation. Methods: CPNs were synthesized via nanoprecipitation using amphiphilic stabilizers (PSMA or PS-PEG-COOH) and characterized for colloidal stability in parenteral solutions. Hemolysis assays were used to assess blood compatibility. Single-dose (0.3 and 1 mg/kg, intravenous) and repeated-dose (0.1–1 mg/kg, intraperitoneal, every 48 h for 28 days) toxicity studies were conducted in BALB/c mice. Hematological, biochemical, histopathological, and biodistribution analyses (via ICP-MS) were performed to evaluate systemic and organ-specific effects. Results: CPNs demonstrated excellent colloidal stability in 5% dextrose, with minimal aggregation. No hemolytic activity was observed at concentrations up to 50 mg/L. Single and repeated administrations revealed no significant changes in body/organ weights, hematological parameters (except transient fibrinogen elevation), or liver/kidney function markers (ALT, AST, BUN, Cr). Histopathology showed preserved tissue architecture in major organs, with mild hepatocyte vacuolation at 30 days. Biodistribution indicated hepatic/splenic accumulation and rapid blood clearance, suggesting hepatobiliary elimination. Conclusions: Platinum porphyrin–doped F8BT CPNs exhibited minimal acute and subacute toxicity, favorable biocompatibility, and no systemic adverse effects in murine models. These findings support their potential as safe PS candidates for PDT. However, chronic toxicity studies are warranted to address long-term organ accumulation and metabolic impacts. This preclinical evaluation provides a critical foundation for advancing CPNs toward clinical applications in oncology. Full article

Artemisia alba Turra is a plant used in folk medicine. Due to its significant polymorphism, there are different chemotypes. This study aimed to characterize the specific chemotypes and evaluate the anti-inflammatory, antioxidant, and antiproliferative potential of an ethanol extract of A. alba Turra aerial parts prepared from plants harvested from the “Alexandru Borza” Botanical Garden, Cluj-Napoca, Romania. The extract phytochemical analysis performed by measuring total polyphenol content (3.4 ± 0.21 mgGAE/g d.w.), total polyphenolic flavonoids (147.12 ± 10.09 mg QE/100 g d.w.), and HPLC-ESI MS polyphenol profiles indicated that in the A. alba Tura extract from the hydroxycinnamic acids chlorogenic acid, caffeoyl tartaric acid, 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, and 4,5-dicaffeoylquinic acid had and from the flavonols, isorhamnetin-rutinoside and rutin had the highest concentration. The extract exhibited good in vitro and in vivo antioxidant activity by reducing oxidants without significant effects on antioxidants. The anti-inflammatory effect tested on rat turpentine oil-induced inflammation was indicated by the reduction in NLRP3 inflammasome markers, NfkB-p65, IL-1β, IL-18, caspase-1, and gasdermin D. The extract had in vitro antiproliferative activity against ovarian tumor cell lines at concentrations from 12.5 to 50 μg/mL, and this mechanism was linked to MDR and NF-κB modulation. A. alba Turra had no liver toxicity and reduced kidney injury associated with inflammation. These findings indicated that this specific Romanian chemotype of A. alba Turra has antioxidant, anti-inflammatory, and antiproliferative properties with potential applications as tumor microenvironment-targeted therapy. Full article

Ammonia and nitrite, as major aquatic pollutants, exhibit significant toxicity toward aquatic organisms. However, their interactive effects on fish are unclear. Aiming to determine their interactive effects, silver carp (Hypophthalmichthys molitrix) were exposed to ammonia, nitrite or ammonia + nitrite for 72 h. Silver carp exhibited pathological damage in the liver and spleen and significant increases in MDA, SOD and CAT in the liver and plasma after ammonia or nitrite exposure. Thus, ammonia and nitrite caused significant histology damage through inducing oxidative stress, and the antioxidative response of SOD−CAT was initiated by silver carp to defend them. A transcriptomic analysis suggested that disruptions in immune responses and metabolism were the main toxic effects caused by ammonia and nitrite. Specifically, nitrite decreased splenic TNF-α and IL-1β but increased splenic C4. Ammonia decreased splenic TNF-α and C4 but increased splenic IL-1β. We noted significant interactions between ammonia and nitrite, and the pathological changes and IBR in the co-exposure groups were less severe than those in the single-factor exposure groups, indicating that ammonia and nitrite have an antagonistic effect. Significant decreases in plasmatic ammonia and NO₂⁻+NO₃⁻ were induced by nitrite and ammonia, respectively. Moreover, the plasmatic glutamine, urea-N, and glutamine synthetase and glutamate dehydrogenase activities increased significantly under ammonia and nitrite exposure, while T-NOS decreased significantly. These results suggest an antagonistic interaction between ammonia and nitrite in silver carp, possibly resulting from competitive bioaccumulation. Consequently, the simultaneous monitoring and control of both ammonia and nitrite concentrations are essential to mitigate their compounded toxic effects, which might be exacerbated under isolated exposure conditions. Full article

Pyrethroid pesticides like deltamethrin and cypermethrin are widely used in aquaculture, yet their food safety implications remain understudied. This research investigated their acute toxicity, tissue-specific bioaccumulation, and elimination patterns in crucian carp (Carassius auratus). Acute toxicity tests determined 96 h LC50 values of 9.68~11.22 ng·mL⁻¹ (deltamethrin) and 3.12~5.01 ng·mL⁻¹ (cypermethrin) with 95% confidence intervals. During 8-day exposures to sublethal concentrations (1/10 and 1/100 of LC50), deltamethrin accumulated predominantly in the liver (peak: 21.98 ng·g⁻¹ at 1.04 ng·mL⁻¹, standard deviation is 0.064 ng·mL⁻¹), whereas cypermethrin concentrated in muscle (peak: 9.76 ng·g⁻¹ at 0.40 ng·mL⁻¹, standard deviation is 0.138 ng·mL⁻¹). A 7-day elimination phase revealed faster clearance of low-concentration residues, with >50% removal within 24 h in all tissues. Bioconcentration factors were highest in the liver (36.62 for deltamethrin) and muscle (45.17 for cypermethrin). These results highlight tissue-specific accumulation risks and rapid initial elimination, providing critical data to optimize pesticide-dosing protocols, mitigate ecotoxicological threats, and enhance food safety in aquaculture systems. Full article

Background: Liver cancer, especially hepatocellular carcinoma, a prevalent malignant tumor of the digestive system, poses significant therapeutic challenges. While traditional chemotherapy can inhibit tumor progression, its clinical application is limited by insufficient efficacy. Hydrophobic therapeutic agents further encounter challenges including low tumor specificity, poor bioavailability, and severe systemic toxicity. This study aimed to develop a liver-targeted, glutathione (GSH)-responsive micellar system to synergistically enhance drug delivery and antitumor efficacy. Methods: A GSH-responsive disulfide bond was chemically synthesized to conjugate glycyrrhetinic acid (GA) with curcumin (Cur) at a molar ratio of 1:1, forming a prodrug Cur-GA (CGA). This prodrug was co-assembled with glycyrrhizic acid (GL) at a 300% w/w loading ratio into micelles. The system was characterized for physicochemical properties, in vitro drug release in PBS (7.4) without GSH and in PBS (5.0) with 0, 5, or 10 mM GSH, cellular uptake in HepG2 cells, and in vivo efficacy in H22 hepatoma-bearing BALB/c mice. Results: The optimized micelles exhibited a hydrodynamic diameter of 157.67 ± 2.14 nm (PDI: 0.20 ± 0.02) and spherical morphology under TEM. The concentration of CUR in micelles can reach 1.04 mg/mL. In vitro release profiles confirmed GSH-dependent drug release, with 67.5% vs. <40% cumulative Cur release observed at 24 h with/without 10 mM GSH. Flow cytometry and high-content imaging revealed 1.8-fold higher cellular uptake of CGA-GL micelles compared to free drug (p < 0.001). In vivo, CGA-GL micelles achieving 3.6-fold higher tumor accumulation than non-targeted controls (p < 0.001), leading to 58.7% tumor volume reduction (p < 0.001). Conclusions: The GA/GL-based micellar system synergistically enhanced efficacy through active targeting and stimuli-responsive release, providing a promising approach to overcome current limitations in hydrophobic drug delivery for hepatocellular carcinoma therapy. Full article

Perfluorooctane sulfonic acid (PFOS) is a persistent organic pollutant that has attracted much attention due to its wide environmental distribution and potential toxicity. Intestinal microbiota is an important regulator of host health, and its composition and metabolic function are easily interfered with by environmental pollutants. In this study, the effects of PFOS exposure on gut microbiota, lipid metabolism, and host health were investigated in mice. The results showed that PFOS exposure did not significantly change α diversity, but significantly affected the β diversity and community structure of intestinal microflora in mice. At the taxonomic level, the ratio of Firmicutes to Bacteroidetes decreased, and the changes in the abundance of specific bacteria were closely related to liver diseases and lipid metabolism disorders. PFOS exposure also interfered with the gut–liver axis mechanism, increased blood lipids and liver function related indicators in mice, and induced intestinal and liver histological lesions. This study revealed the toxic mechanism of PFOS mediated by intestinal microbiota, providing a new research perspective for health problems caused by environmental pollutants and theoretical support for the formulation of relevant public health policies. Full article

Background/Objectives: Infliximab, ipilimumab, and nivolumab are three monoclonal antibodies that have been associated with hepatotoxicity. Three separate physiologically based pharmacokinetic (PBPK) models were developed in GastroPlus^® to simulate plasma and liver concentrations in patient populations after administration of either infliximab, ipilimumab, or nivolumab. Methods: The models include distribution and clearance mechanisms specific to large molecules, FcRn binding dynamics, and target-mediated drug disposition (TNF-α for infliximab, CTLA-4 for ipilimumab, and PD-1 for nivolumab). Results: The PBPK model for each large molecule was able to reproduce observed plasma concentration data in patient populations, including patients with rheumatoid arthritis and patients with solid tumors. Liver concentrations were predicted to be between 10% and 23% of the plasma concentrations for each of the three drugs, aligning with previously reported results. This lends further validity to the PBPK models and their ability to accurately predict hepatic concentrations in the absence of direct tissue measurements. Conclusions: These results can be used to drive liver toxicity predictions using the quantitative systems toxicology model, BIOLOGXsym™, which integrates hepatic interstitial concentrations with in vitro mechanistic toxicity data to predict the extent of liver toxicity for biologics. Full article