Journal of Applied Toxicology最新文献

{"title":"Comparative Developmental Toxicity of Roxithromycin in Danio rerio and Xenopus laevis.","authors":"Harika Eylül Esmer Duruel, Duygu Ozhan Turhan, Murat Ozmen, Abbas Güngördü","doi":"10.1002/jat.70004","DOIUrl":"10.1002/jat.70004","url":null,"abstract":"<p><p>Antibiotics are among the most frequently detected pharmaceuticals in aquatic environments, raising concern about their effects on nontarget organisms. Roxithromycin (ROX), a semisynthetic macrolide widely used in human medicine, occurs in wastewater and surface waters, yet its developmental and biochemical impacts on aquatic vertebrates remain poorly understood. Here, we comparatively assessed the sublethal toxicity of ROX in zebrafish (Danio rerio) and frog (Xenopus laevis) embryos using standardized assays. Embryos were exposed for 96 h to nominal concentrations of 88-1000 mg/L. No lethality occurred in either species. However, zebrafish exhibited high malformation rates (46%-92%), dominated by pericardial edema and spinal curvature, and a marked reduction in heart rate within 24 h. In contrast, X. laevis displayed lower and non-dose-dependent malformations (≤ 19%), mainly gut and abdominal edema. Biochemical markers revealed distinct species-specific responses: In zebrafish, only glutathione (GSH) increased at the highest concentration, whereas in X. laevis, glutathione S-transferase (GST) and GSH increased at all concentrations, glutathione reductase (GR) was inhibited, and catalase (CAT) decreased at the highest concentration. UV-Vis analyses confirmed that ROX remained mostly undissolved, with acid-conditional values representing analytical upper bound estimates rather than true dissolved concentrations. Accordingly, exposures are interpreted as suspensions with limited dissolved fractions. These findings show that zebrafish are more prone to cardiac and morphological disruption, while X. laevis exhibits stronger biochemical stress responses. Overall, the study highlights the ecological relevance of macrolide antibiotics and supports the use of cross-species testing in environmental risk assessment of pharmaceuticals in aquatic ecosystems.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":"1963-1976"},"PeriodicalIF":2.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145634025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rosiglitazone Mitigates Valproic Acid-Induced Neurotoxicity in Zebrafish Larvae via Activation of the PPAR Pathway.","authors":"Jian Guo, Naying Zheng, Junyu Liang, Yang Jiang, Jingwen Li, Chengyong He, Xuefeng Wang","doi":"10.1002/jat.70031","DOIUrl":"10.1002/jat.70031","url":null,"abstract":"<p><p>Valproic acid (VPA), a commonly used treatment for epilepsy and psychiatric disorders, is associated with neurodevelopmental toxicity and an elevated risk of autism spectrum disorder (ASD). This study investigates the protective effects of rosiglitazone (RGZ), a peroxisome proliferator-activated receptor (PPAR) agonist, against VPA-induced neurotoxicity in zebrafish larvae. Zebrafish embryos were exposed to VPA (50, 75, 100 μM) from 0.5-h postfertilization (hpf) to 120 hpf, with or without RGZ cotreatment. VPA exposure significantly reduced locomotor activity, evidenced by decreased swimming distance and velocity, and disrupted neurotransmitter homeostasis, with elevated norepinephrine and L-glutamic acid levels. Transcriptomic analysis and qRT-PCR revealed that VPA downregulated PPAR pathway genes (ppara, pparg, pck1, and fabp1), while RGZ cotreatment partially restored locomotor activity, normalized neurotransmitter levels, and rescued PPAR pathway gene expression. These findings demonstrate that RGZ mitigates VPA-induced neurotoxicity by activating PPAR signaling, restoring metabolic balance, and improving motor function, suggesting PPAR agonists as potential therapeutic agents for VPA-induced neurotoxicity and ASD-related deficits.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":"2158-2166"},"PeriodicalIF":2.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145701197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolomics-Based Insights Into the Toxicological Effects and Mechanisms of Microplastics: A Comprehensive Review.","authors":"Ziyue Wang, Sixuan Lu, Yan Ma, Yuanteng Sun, Rongli Sun","doi":"10.1002/jat.70077","DOIUrl":"10.1002/jat.70077","url":null,"abstract":"<p><p>Microplastics (MPs), a pervasive environmental pollutant, present a significant and growing threat to human health. Metabolomics has emerged as a powerful tool for deciphering pollutant toxicity by sensitively detecting metabolic perturbations. This review outlines metabolomic methodologies and their application in environmental toxicology. Meanwhile, evidence of the multisystem toxic effects of MPs revealed by metabolomics is synthesized, and progress in integrating metabolomic data with multiomics to elucidate underlying mechanisms is summarized. Results indicate that MPs induce systemic toxicity through organ-specific metabolic disruptions. In the intestinal tract, MPs compromise barrier integrity, induce amino acid and lipid metabolic reprogramming, and cause microbial dysbiosis, impacting distal organs via the gut-organ axes. Upon entering the nervous system, they disrupt neurotransmitter metabolism and impair cognitive function. Concurrently, MPs impair reproductive function by altering testicular phospholipid metabolism, reducing sperm quality, and disrupting placental lysine and glucose homeostasis, restricting fetal growth. Furthermore, MPs inhibit central energy metabolism pathways, including glycolysis and the tricarboxylic acid cycle across diverse species, resulting in impaired growth and development. Future research should leverage spatial metabolomics, causal validation techniques, and advanced computational algorithms to systematically map MP-induced metabolic disruptions, establish definitive mechanistic links, and reconstruct toxicity networks. Our study provides scientific basis for further clarifying the MP toxicity and identifying molecular targets of metabolic reprogramming to develop interventions that mitigate the health risks of MPs.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":"1723-1749"},"PeriodicalIF":2.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147306398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epicuticular Wax Disruption as a Novel Mechanistic Strategy to Enhance Insecticidal Toxicity Against Aleurodicus dispersus on Eggplant and Cassava.","authors":"T Boopathi, N Anusha, J G Prasuna, K Divya","doi":"10.1002/jat.70001","DOIUrl":"10.1002/jat.70001","url":null,"abstract":"<p><p>The epicuticular wax layer in Aleurodicus dispersus (spiraling whitefly) serves as a hydrophobic barrier that limits insecticide penetration and contact toxicity. This study evaluated the potential of solvent, enzymatic, and natural agents to disrupt the wax layer and enhance insecticidal efficacy. Laboratory assays screened eight agents-chloroform, hexane, ethyl alcohol, xylene, salt solution, soap solution, lipase, and CTCRI cassava extract-across graded concentrations. Two-way ANOVA revealed significant main effects of solvent type (F₇,₇₀ = 10.697; p ≤ 0.01) and concentration (F_10,70 = 40.936; p ≤ 0.01) on percent wax removal. Lipase (0.5-2.5 g/L) and soap solution (1.5-10 g/L) exhibited the highest efficacy, confirmed through validation bioassays and Tukey's HSD grouping (p ≤ 0.01). Pot trials on eggplant (Solanum melongena) and cassava (Manihot esculenta) demonstrated that wax disruption substantially increased toxicological performance. Lipase and soap solution alone reduced whitefly density by 40%-55%, while combinations with botanicals (neem seed kernel extract [NSKE], azadirachtin) achieved 70%-90% mortality. Integration with triazophos or acephate resulted in near-total suppression (95%-100% mortality; ≤ 4 insects/leaf). Three-way ANOVA (p ≤ 0.01) confirmed significant treatment and interaction effects on both whitefly population and corrected mortality, indicating enhanced penetration and bioavailability of insecticides through wax dissolution. These results introduce epicuticular wax disruption as a mechanistic adjuvant approach in insect toxicology. Lipase and soap solution emerge as potent surface-active agents for improving insecticidal delivery and contact toxicity, offering a new direction in formulation science and integrated pest management.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":"1907-1917"},"PeriodicalIF":2.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145604237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Health Implications of Industrial Pollution: A Study of Physiological Parameters and Oxidative Markers in Workers in Erbil City.","authors":"Rayan Sardar Sulaiman, Edrees Mohammad Ameen","doi":"10.1002/jat.70005","DOIUrl":"10.1002/jat.70005","url":null,"abstract":"<p><p>One of the largest contributors to industrial pollution worldwide is the steel sector, which also poses a significant risk to the health of its employees. In contrast to a control group that was not exposed, this study examined the physiological and oxidative stress effects of industrial pollution on employees at the Darin Steel Company in Erbil City. Assessments of cardiovascular parameters (blood pressure and heart rate), respiratory function (forced vital capacity and arterial oxygen), fasting blood sugar, HbA1c, liver and kidney function tests, and oxidative stress biomarkers malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and superoxide dismutase (SOD) were conducted on 75 male employees and 25 healthy male controls. Airborne pollutant levels were significantly elevated across all workplace units compared with the control group, with the highest concentrations observed in the furnace and scrap units. Particulate matter (PM2.5) rose from 3.29 μg/m³ in the control to 65.78 μg/m³ in the furnace unit, and similar increases were seen for particulate matter (PM10), carbon monoxide (CO), nitrogen dioxide (NO₂), and sulfur dioxide (SO₂). The findings showed that exposed workers experienced severe adverse effects, including decreased forced vital capacity (FVC), increased systolic and diastolic blood pressure, fasting blood sugar, and compromised liver and kidney function. The impacts were worse for workers in high-exposure locations (scrap units and furnaces). Workers' antioxidant SOD levels were lower, and oxidative stress markers (MDA ands 8-OHdG) were significantly greater, indicating cellular oxidative stress and DNA damage. These health impacts were worsened by exposure times longer than 4 years. The results highlight the adverse health effects of industrial pollution, particularly in areas with high exposure levels, and the role that oxidative stress plays in the organ damage caused by pollution. This study provides important new insights for occupational health treatments designed to mitigate the risks associated with pollution in industrial environments.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":"2034-2049"},"PeriodicalIF":2.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145648575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Toxicity of Impurities of Illicit Heroin in Rats.","authors":"Ali Kargar, Jalal Hassan, Mohammad Kazem Koohi, Hadi Shirzad, Soheila Adeli, Abdullah Amini, Javad Fahanik Babaei, Samad Shokouhi Rad","doi":"10.1002/jat.4991","DOIUrl":"10.1002/jat.4991","url":null,"abstract":"<p><p>The present study aimed to investigate the chemical composition of heroin samples available in the Iranian illicit market and evaluate their toxic effects on brain and liver tissues in an animal model. Different heroin samples were analyzed using gas chromatography and classified into four distinct groups, labeled A, B, C, and D, based on the presence of pharmaceutical additives such as acetaminophen, caffeine, and dextromethorphan. Subsequently, male Wistar rats were treated with these compounds using standard addiction induction models. After the treatment period, the brain and liver tissues of the animals were subjected to pathological and biochemical examinations. The results showed that each type of heroin had a specific pattern of tissue toxicity, and the extent of brain and liver damage varied among the groups. The findings of this research emphasize the importance of accurately identifying the composition of heroin available in the market and its impact on consumers' health, which can serve as a basis for preventive measures and harm reduction policies related to substance abuse.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":"1939-1950"},"PeriodicalIF":2.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145604343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Excessive Use of Polygonatum sibiricum Causes No Acute Lethality but Induces Multiple Toxic Effects in Mice.","authors":"Juzuo Zhang, Fenfang Zhang, Shunqing Wang, Pan Li, Xiang Jian, Lin Shu, Naxin Zhang, Wenhu Zhou, Junfei Xu","doi":"10.1002/jat.70013","DOIUrl":"10.1002/jat.70013","url":null,"abstract":"<p><p>Polygonatum sibiricum Delar. ex Redoute (P. sibiricum) is a traditional Chinese medicine with multiple health benefits in medicinal-edible dual consumption. However, its toxicological profiles and underlying mechanisms remain poorly characterized, limiting its safe clinical and dietary applications. In this study, an ethanolic extract of P. sibiricum (PS) was obtained via a microwave-assisted ethanol extraction method, and the flavonoid and saponin contents were quantitatively determined via colorimetric assays and high-performance liquid chromatography (HPLC). After oral administration to mouse models, the main blood-accessible constituents, acute, subacute and genetic toxicities, and potential mechanisms were systematically evaluated via HPLC, manifestation observations, routine blood tests, histopathological evaluations, and network toxicology analyses. The results demonstrated that the PS contained 1.138-mg/ml flavonoids and 9.152-mg/ml saponins. Approximately 10 blood-accessible constituents among 15 components were discovered, including diosgenin, 3'-methoxydaidzein, baicalein, (2R)-7-hydroxy-2-(4-hydroxyphenyl) chroman-4-one, 4',5-dihydroxyflavone, (+)-syringaresinol-O-beta-D-glucoside, zhonghualiaoine 1, methylprotodioscin_qt, sibiricoside A_qt and β-sitosterol. Although PS did not cause acute lethality, high-dose exposure induced obvious behavioural changes and chromosomal damage. Subacute administration elicited time-dependent biochemical disturbances and structural lesions in the liver, kidney and spleen. Bioinformatic results linked hepatotoxicity to PI3K-AKT signalling, nephrotoxicity to HIF-1 and MAPK cascades, and splenotoxicity to convergent PI3K-AKT, NF-κB and MAPK pathways. Molecular docking revealed robust interactions between PS constituents and the predicted toxicity-related targets. Taken together, these findings suggest that PS is nonlethal but potentially has genetic and multiorgan toxicities. Multitarget and multipathway mechanisms are involved in PS-induced toxicities. These findings provide a comprehensive toxicological reference for the rational and safe use of P. sibiricum in both medicine and diet.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":"2106-2123"},"PeriodicalIF":2.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatotoxicity Mechanisms of Sirolimus and Everolimus Unveiled Through Metabolomics and Transcriptomics Analysis.","authors":"Zixin Zhang, Yingying Tang, Rongjing Xing, Wenjing Liao, Tong Qiu, Jiangyuan Zhou, Xuepeng Zhang, Xue Gong, Yuru Lan, Shanshan Xiang, Siyuan Chen, Yi Ji","doi":"10.1002/jat.70012","DOIUrl":"10.1002/jat.70012","url":null,"abstract":"<p><p>Sirolimus and everolimus, two representative inhibitors of the mammalian target of rapamycin (mTOR), have distinct therapeutic effects on numerous paediatric diseases that do not have specific treatments, particularly vascular abnormalities, but their safety regarding the growth and development of children is still worth considering. The most frequent adverse reaction in clinical practice, elevated liver enzymes, has not yet been thoroughly investigated to determine whether it is hepatotoxic to growth and development. In this study, experiments with zebrafish models revealed that sirolimus and everolimus caused hepatotoxicity, on the basis of the delayed rate of yolk sac absorption, even at a standard dose (≤ 0.1 μM). At high concentrations (≥ 0.5 μM), more pronounced hepatotoxic effects were observed, including significant reductions in liver size, elevated ALT levels, widened gaps between hepatocytes and increased vacuolization within hepatocytes, as assessed by liver morphology, functional biomarkers and histopathology. Integrated transcriptomic and metabolomic analyses revealed that the hepatotoxicity was associated with aberrant activation of the PI3K/AKT pathway and disrupted lipid metabolism, primarily driven by downregulation of phosphoenolpyruvate carboxykinase 1 (PCK1). These findings underscore the importance of regular monitoring of drug blood concentrations in paediatric patients and provide new insights into dose optimization and toxicity surveillance in children.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":"2050-2064"},"PeriodicalIF":2.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145648610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic Low-Dose Unsymmetrical Dimethylhydrazine Exposure in Rats: Multiorgan Mechanisms and Biomarker Identification.","authors":"Fuzhou Liu, Bing Liu, Keli Wang, Xiaoyu Wang, Zhen Sun, Xiaojuan Pan, Zengming Zhao","doi":"10.1002/jat.70008","DOIUrl":"10.1002/jat.70008","url":null,"abstract":"<p><p>Unsymmetrical dimethylhydrazine (UDMH), a highly toxic rocket propellant with known multiorgan effects, requires urgent characterization of its chronic low-dose toxicity. Using an integrated approach including exploratory transcriptomics (n = 3/group) and metabolomic (n = 4/group) approaches in male Sprague-Dawley rats exposed to high-dose UDMH concentrations (100 ppm (v/v), 4 h/day, 5 days/week for 60 days), we delineated organ-specific injury mechanisms and identified candidate systemic biomarkers. Histopathological assessment revealed significant pulmonary injury (62.5% incidence of focal hemorrhage, p = 0.015; inflammatory focus density: 8.3 ± 1.7 foci/mm²) and renal injury (tubular basophilia index: 1.8 ± 0.4, p < 0.001). Integrated multiomics analysis identified a mechanistically interconnected biomarker triad: (1) hepatic Cyp4a1 upregulation (log₂FC = 4.7), indicating PPARα-mediated adaptive detoxification; (2) elevated serum taurine (1.27-fold, p < 0.05), reflecting mitochondrial compensatory responses; and (3) increased urinary L-DOPA (3.1-fold, false discovery rate [FDR] < 0.05), signifying neuroendocrine dysregulation. Together, these core biomarkers delineate the pathophysiology of chronic UDMH toxicity, characterized by PPARα-driven detoxification intersecting with mitochondrial stress adaptation and catecholaminergic disruption across organ systems. To our knowledge, this is the first integrated multiomics study of chronic UDMH exposure, establishing a mechanistic framework for toxicity and highlighting pulmonary-renal pathology, serum taurine, and hepatic Cyp4a1 as key indicators for developing future risk assessment strategies.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":"1987-2002"},"PeriodicalIF":2.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13136406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145634046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histopathological and Molecular Alterations in the Liver of Hoplias intermedius (Pisces: Erythrinidae) Contaminated by Heavy Metals in a Neotropical River.","authors":"Gabriel Eric Rodrigues Arêdes, Breno Thuller, Yves Moreira Ribeiro, Elizete Rizzo, Nilo Bazzoli, Alessandro Loureiro Paschoalini","doi":"10.1002/jat.70007","DOIUrl":"10.1002/jat.70007","url":null,"abstract":"<p><p>Heavy metals, originating from human activities and natural processes, are a threat to aquatic organisms and the environment. As the main organ responsible for detoxification, the liver plays a fundamental role in regulating potentially harmful chemicals such as heavy metals, and the interaction between heat shock protein 70 and metallothionein may be important in processes related to cellular protection, since both participate in responses to oxidative stress and redox balance. To analyze the effects of heavy metals on the morphology and biomarkers expression in the liver of Hoplias intermedius, specimens from the Paraopeba River-contaminated environment and Abaete River-control environment were collected, and fragments of liver were sampled for histopathological and immunohistochemical analyses. Additionally, the levels of Al, Cd, Pb, Cu, Cr, Fe, Mn, and Zn were measured in water and liver from all individuals. The results showed concentrations above the permitted levels of Al, Cd, and Mn in the water, and Cd, Pb, Cr, and Fe in liver samples of Paraopeba River. Furthermore, dilatation and congestion of sinusoidal capillaries and lobular veins were observed; vacuolization of hepatocytes; formation of melanomacrophage centers; and signs of tissue necrosis were detected. In immunohistochemical analysis, metallothionein and heat shock proteins (HSP70) markings increased when compared to fish from the control environment. These results indicate the severity of the toxic effects of chronic exposure to heavy metals on aquatic biota, and a possible human health threat due to the consumption of contaminated fish.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":"1927-1938"},"PeriodicalIF":2.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145604313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}