Pharmaceuticals and illicit drugs are environmental contaminants of concern due to their persistence and health impacts. Whilst spatial and temporal patterns have been extensively studied, seasonal variations remain under-explored globally. This review examined studies across six continents, synthesising wastewater and surface water data to identify seasonal patterns. Rather than a uniform global trend, seasonal peaks are continent- and matrix-specific. In Europe, effluent concentrations were highest in summer, whereas in influent higher concentrations were more frequently observed in winter. Asia exhibited elevated autumn concentrations in influent and effluent wastewaters, while surface water loads peaked in winter. North America influent concentrations were highest in summer. Africa showed higher summer wastewater loads and winter peaks in surface waters. Data from Oceania and South America was comparatively limited. Seasonal differences may reflect interacting climatic and hydrological conditions, population dynamics, environmental degradation, and wastewater treatment highlighting the need for regionally and seasonally tailored monitoring strategies.
Environmental factors, such as temperature, exert a critical influence on aquatic ecosystems. It is important to assess how climate change and pollutants affect contaminants released into water. In this study, the combined effects of environmentally relevant temperature variation, polystyrene microplastics (PSMPs), and copper were evaluated in zebrafish. Toxicity tests were conducted at 23, 26, and 29°C. The PSMPs were aged via the Fenton reaction, to simulate environmental oxidative conditions. Temperature influenced embryonic development, with hatching strongly delayed at 23 °C, while contaminant-related effects exhibited variability at 26 and 29 °C. The combination of aged PSMPs and Cu²⁺ produced pronounced effects on hatching and increased mortality under thermal conditions, particularly at 29 °C. Swimming activity showed significant temperature-dependent alterations, with interactions between developmental temperature and contaminant exposure for swimming distance and velocity. These findings highlight the importance of considering temperature when assessing the effects of microplastics and metals on fish development.
Seals accumulate xenobiotics through dietary biomagnification and exposure to polluted marine environments, with contaminants concentrating in their blubber. Biotransformation mitigates xenobiotic toxicity by converting lipophilic compounds into excretable hydrophilic metabolites, a process coordinated by nuclear receptors including the Pregnane X Receptor (PXR), whose plastic ligand-binding domain enables broad xenobiotic sensing. By examining PXR in pinnipeds, we investigated the evolutionary conservation and functional characterization of PXR using genomic sequence analysis, protein structural prediction, and transactivation assays, revealing broadly conserved structural features alongside species-specific functional divergence in receptor responsiveness to environmental stressors. Specifically, the obtained results highlight divergent gene and functional landscapes with ORF-disrupting mutations identified in Monachus monachus and Neomonachus schauinslandi that abolish receptor activation toward known PXR ligands. In contrast, Leptonychotes weddelli retained an intact PXR ORF but showed reduced receptor activity, revealing functional divergence in PXR among pinnipeds.
Micro- and nanoplastics (MNPs) represent an emerging class of contaminants, yet their biological impacts remain poorly understood. Mechanistic research comparing polymers such as polypropylene (PP) and polyethylene terephthalate (PET) is challenging because of strong differences in hydrophobicity, buoyancy or sedimentation behavior, size distribution (aggregation) and lack of strong acute cytotoxic effects. This study introduces an innovative in vitro dosing platform with 3D hepatic spheroids, providing a dosimetrically robust model to investigate metabolic and bioenergetic effects of chronic MNP exposure. Gel encapsulation was used to expose spheroids for up to 21 days to MNPs of different composition and size. MNPs accumulated in spheroids with polymer-specific localization. Cytotoxicity was limited, but metabolic profiling revealed consistent bioenergetic shifts. This work highlights the importance of particle size distributions and introduces alginate bead encapsulation as a reproducible dosing strategy for comparing MNPs and defining toxic doses linked to biologically relevant molecular and cellular events.
OBJECTIVE:Occupational lead exposure may cause renal toxicity; however, the renal effects of calcium disodium ethylenediaminetetraacetic acid (CaNa₂EDTA) chelation therapy remain unclear. This study evaluated short-term renal function changes and urinary findings in workers undergoing CaNa₂EDTA chelation for occupational lead exposure. METHODS:This retrospective study included 245 male workers with occupational lead exposure who received CaNa₂EDTA chelation therapy between January 2022 and January 2026. Urinary protein, albumin, and 24-hour urinary lead excretion were assessed on day 3, while post-treatment blood lead levels and renal function parameters were assessed on day 6. RESULTS:Blood lead levels significantly decreased after chelation therapy (p < 0.001). Urea levels decreased, whereas serum creatinine levels increased slightly and eGFR values declined significantly (all p < 0.001). Proteinuria and albuminuria were detected in 40.8% and 28.2% of patients, respectively. Employment in other occupational sectors was associated with higher odds of proteinuria, but not albuminuria, after adjustment. CONCLUSION:CaNa₂EDTA effectively reduced blood lead levels, while small changes in renal function and urinary abnormalities were observed during treatment; however, these findings cannot be attributed specifically to chelation therapy.
Bisphenol A (BPA) is a pervasive endocrine-disrupting chemical with documented toxic effects in living organisms. This study evaluated the protective potential of vanillic acid (VA) against BPA-induced toxicity in Drosophila melanogaster. BPA exposure elevated lipid peroxidation (MDA), reduced antioxidant defenses (SOD and CAT activities and GSH content), increased DNA damage (Comet assay), lowered acetylcholinesterase levels, and impaired developmental parameters (pupation, climbing, crawling, lifespan, and food intake). BPA also upregulated SOD, CAT, gclc, hsp70, CncC, and Keap1 mRNA expression, indicating activation of the cellular stress response. VA co-treatment dose-dependently mitigated these effects, restoring redox balance, reducing DNA strand breaks at the highest VA dose, and rescuing developmental endpoints. These findings suggest that VA is an effective natural protective agent against BPA toxicity in vivo, an effect accompanied by modulation of CncC/Keap1 pathway gene expression.
Lead is a systemic toxic agent, and occupational exposure remains a serious public health problem. A search of PubMed, Scopus, and Web of Science identified English-language studies published between 2015 and 2025 that included research assessing oxidative stress biomarkers and essential metals in adults occupationally exposed to lead. 45 studies with 7 314 participants were included. The findings demonstrate that occupational lead exposure increases reactive oxygen species production and oxidative damage (as evidenced by elevated levels of malondialdehyde, lipid hydroperoxides, and 8-OHdG). Concurrently, lead disrupts essential metal homeostasis (as reflected by reduced levels of zinc, calcium, magnesium, selenium, and copper). Occupational lead exposure induces oxidative stress, increases the number of DNA strand breaks and disruption of essential metal balance. Despite consistent evidence, limitations such as cross-sectional study designs, underrepresentation of female workers, and insufficient evaluation of mixed-metal exposure persist. These findings underscore the need for integrated biomonitoring of toxic and essential elements and for longitudinal studies to better inform prevention strategies and long-term risk assessment.
Phthalate esters (PAEs) are environmental pollutants with potential neuroendocrine effects, yet systematic comparisons across congeners remain scarce. We employed electrostatic potential analysis (ESP), network toxicology, molecular docking, and molecular dynamics with MM-PBSA (Molecular Mechanics Poisson-Boltzmann Surface Area) binding free energy calculations to evaluate six PAEs. Target prediction from public databases and neuroendocrine-related gene compilation yielded 176 common genes, identifying five hubs AKT1, ESR1, MAPK3, PPARG, and TNF-α. MM-PBSA binding energies ranged from -40.23 to -8.25 kcal/mol, with DINP binding strongest to ESR1 and DEHP exhibiting the highest affinities to PPARG and TNF-α. ESP revealed congener-specific surface properties, with DEP and DIBP exhibiting strong negative potentials on carbonyl oxygens, whereas DEHP and DINP were predominantly hydrophobic. We propose a tentative in silico hierarchy with DEHP > BBP ≈ DBP > DINP > DIBP > DEP. This work provides a theoretical basis for congener specific risk assessment of PAEs.
Parabens (PBs) are widely used preservatives in consumer products and suspected endocrine disruptors associated with adverse pregnancy outcomes. However, a structured framework for quantifying these risks is currently lacking. Employing the Targeted Risk Assessment of Environmental Chemicals (TRAEC) scheme, this study synthesized evidence from 16 epidemiological, 11 in vivo, and 5 in vitro studies, alongside our experimental data. PBs posed a moderate overall risk (score: 6.07), displaying compound-specific profiles. Regarding placental toxicity, methylparaben (MePB) scored highest (6.83), outranking ethylparaben (EtPB: 5.94), propylparaben (PrPB: 5.05), and butylparaben (BuPB: 3.17), whereas MePB (6.67) and BuPB (6.60) dominated birth outcome risks. Literature associated PBs with shortened gestation, restricted fetal growth, thyroid disruption, and metabolic alterations. Mechanistically, our in vitro human trophoblast models demonstrated that MePB and PrPB suppressed cellular proliferation, migration, and tube formation, driving placental insufficiency. These insights underscore the critical need to mitigate maternal PBs exposure to protect fetal-placental health.
Studies have shown that fluoride induces cartilage damage, however, the specific mechanism is unknown. In this study, we investigated the effect of fluoride on extracellular matrix metabolism and its molecular regulatory mechanism, using well-established experimental models SW1353 cell line and neonatal rat tibia organ culture. We found that 5 × 10-4 M fluoride reduced proteoglycan synthesis by 20%, significantly downregulated the expression levels of Aggrecan, Collagen Type II and X Alpha 1 Chain, and upregulated various matrix metalloproteinases. Based on RNA sequencing results, we found that differentially expressed genes were significantly enriched in the hypoxia inducible factor 1 (HIF1) signaling pathway, which ranked second in enrichment significance. Further studies demonstrated that fluoride significantly suppressed the expression of glycolysis-related enzymes, the oxygen consumption rate and glycolytic capacity, leading to notably reduced ATP production. Moreover, fluoride decreased both mRNA and protein level of HIF1α by half through increasing prolyl hydroxylase domain 2 expression by twice. Importantly, stabilizing HIF1α with CoCl2 effectively reversed the adverse effects of fluoride. Together, these results suggested that fluoride inhibited glycolytic activity by the PHD2/HIF1α signaling pathway, thereby further disrupting the metabolic balance of the cartilage extracellular matrix.
Air pollution and undernutrition are major global health problems that frequently coexist in vulnerable populations and may interact to impair pulmonary immune defenses. We investigated how chronic undernutrition influences alveolar macrophage (AM) responses to subchronic particulate matter (PM) exposure and their subsequent responsiveness to a viral-like stimulus. Male Wistar rats were assigned to control or nutritional growth retardation (NGR) groups, either ad libitum feeding or a 20% caloric restriction for 4 weeks, respectively. During this period, animals received intranasal Residual Oil Fly Ash (ROFA), a surrogate for airborne PM, or vehicle. Isolated AMs were evaluated for viability, TNFα production, oxidative stress, Nrf2 and LC3 expression, and subsequently challenged with Poly (I:C), a synthetic analog of viral double-stranded RNA. Under basal conditions, AMs from NGR animals exhibited reduced viability and Nrf2 expression, increased TNFα secretion, and elevated LC3 expression compared with controls. In well-nourished animals, ROFA induced similar alterations. However, ROFA produced little or no additional effect in NGR-AMs, indicating an attenuated responsiveness to PM exposure. Following Poly (I:C) stimulation, control AMs mounted an inflammatory response that was further enhanced by prior ROFA exposure, whereas AM from NGR animals displayed an impaired response regardless of ROFA exposure. These findings suggest that chronic undernutrition alters basal AM function and modifies their responsiveness to both PM and subsequent viral-like stimulation. This impaired adaptability may influence innate pulmonary immune defenses and increase susceptibility to respiratory infections in populations simultaneously exposed to undernutrition and air pollution.
Freshwater ecosystems are increasingly contaminated by neuroactive compounds, including lithium (Li) from battery waste and curcumin (CUR) from consumer products, but their sublethal effects on aquatic invertebrates are poorly characterized. Linking behavioral alterations to biochemical responses under sublethal exposure remains a challenge. We used Girardia tigrina to assess behavioral and redox responses to mechanical, photic, and predator odor stress, followed by Li or CUR treatment. Mechanical and predator-odor stress increased time in the illuminated compartment by 40-60% (p < 0.0001), whereas light stress decreased it by ~35% (p < 0.001). CUR shifted responses toward control levels across all stressors (p > 0.05 vs. controls), while Li showed persistent effects under mechanical and predator-odor stress (p < 0.05). SOD activity increased 1.5-2.0-fold (p < 0.01); GST was reduced by stress and further decreased by treatments (p < 0.05). These findings support G. tigrina as a model for sublethal neurotoxicity.
Dapsone possesses anti-infective and anti-imflammatory properties, but its CYP-mediated metabolism to hydroxylamines causes dose-dependent haematological toxicity which impairs patient tolerance. In the 1990s cimetidine-mediated partial inhibition of the oxidative metabolism of dapsone was demonstrated clinically to lower methaemoglobin formation and subsequent case studies with fragile and immunosuppressed patients with multiple complex pathologies, showed cimetidine could minimize dapsone-mediated methaemoglobin formation in the place of methylene blue, when G6PD status is unknown, is deficient or there is prior sensitization. Pre-clinical and in vitro studies also suggest that prior administration of the antioxidant α-lipoic acid may potentially augment cimetidine's attenuation of dapsone-mediated methaemoglobin's formation through its conversion to dihydrolipoic acid which can restrict methaemoglobin formation within the erythrocyte. Overall, combined with novel buccal dapsone formulations which avoid first-pass metabolism, concomitant α-lipoic acid may augment cimetidine-mediated amelioration of dapsone's- haematological toxicity, potentially promoting the drug's patient tolerance and clinical utility.
Glyphosate is one of the most widely used herbicides in agriculture. Although it has long been considered relatively harmless to animals, increasing attention has recently been paid to its potential nephrotoxic effect. Therefore, the aim of the present study was to investigate the impact of chronic glyphosate intoxication on renal function in rats and to evaluate the nephroprotective effects of C60 fullerenes as potent antioxidants. Chronic glyphosate exposure (daily dose of 10 mg/kg for 16 weeks) was found to impair renal function, as evidenced by increased biochemical indicators. Administration of water-soluble C60 fullerenes (daily dose of 1 mg/kg) partially improved the studied biochemical parameters, namely by 16-35 ± 2%, which was further confirmed by histopathological analysis of kidney tissues. These findings suggest that C60 fullerenes may be considered promising nanomaterials for correcting renal dysfunction caused by chronic glyphosate intoxication.
Isoflurane is a potent greenhouse gas and a significant occupational hazard in veterinary operating rooms (VORs) lacking scavenging systems. This study performed a novel, integrated and complementary exposure assessment during large-animal anesthesia by measuring ambient air concentrations, personal breathing zone levels (badges), and internal biological doses (urinary isoflurane). Additionally, data from small- and large-animal VORs were consolidated to characterize institution-wide indoor pollution within the monitored surgical environments. Ambient concentrations were measured via infrared gas analyzer, while badges and post-shift urine samples were analyzed by GC and GC-MS, respectively. Results revealed high residual concentrations exceeding the NIOSH Recommended Exposure Limit. Large-animal anesthesiologists had mean exposures of 9 ± 1 ppm (badges) and median urinary isoflurane concentrations of 32 μg/L, demonstrating that both markers were consistent with high exposure. These findings emphasize the implementation of effective scavenging and ventilation systems in veterinary settings, particularly in resource-limited regions, to safeguard occupational health and mitigate the environmental impact of anesthetic emissions.
BACKGROUND:Podophyllotoxin (PPT) has antitumour activity but may cause nephrotoxicity through incompletely defined mechanisms. METHODS:Male Sprague-Dawley rats received oral PPT (5 or 10 mg/kg/day) for 5 days. Renal injury was evaluated by biochemical, histopathological, Raman, metabolomic, transcriptomic, targeted proteomic, and molecular analyses, followed by validation in NRK-52E cells. RESULTS:PPT at 10 mg/kg reduced 24-h urine output (p < 0.05) and increased serum urea (p < 0.05), uric acid (p < 0.001), KIM-1 (p < 0.001), and lipocalin-2 (p < 0.0001). Renal GSH and CAT decreased (p < 0.001 and p < 0.01, respectively), accompanied by tubular injury, collagen deposition, and apoptosis. Trpm2 and inflammatory and matrix-remodelling genes were upregulated. PRM identified reduced LDHC, HK3, and MGST2 abundance. JNJ-28583113 attenuated PPT-induced ROS accumulation, apoptosis, Nod1/Nod2 expression, and NF-κB p65 phosphorylation. CONCLUSION:PPT induces subacute kidney injury involving oxidative stress and TRPM2-NOD-NF-κB-related inflammatory signalling.
To address the global need for quantitative and sensitive methods to monitor the effects of chemical stress, we introduce a rapid, non-destructive impedimetric biosensor that uses in vitro cell-based systems as the biorecognition element and diazinon, an organophosphorus pesticide, as the model chemical for assessing stress. The study aimed to evaluate the biosensor's sensitivity and effectiveness relative to established in vitro cytotoxicity assays. Light microscopy confirmed cell density and viability on the electrodes, while electrochemical impedance spectroscopy (EIS) revealed a linear, concentration-dependent decrease in impedance following diazinon exposure. Crucially, the EIS biosensor demonstrated significantly lower effective concentrations (EC50 = 0.079 mM, EC20 = 0.012 mM, EC10 = 0.006 mM) than in conventional assays, which proves that our biosensor detects an earlier toxicological event. We conclude that the cell-based impedimetric biosensor provides a label-free platform for non-destructive assessment of the effects of aquatic contaminants.
