Batuhan Bilgin, Mehmet Tahir Husunet, Ibrahim Halil Kenger
{"title":"Cytogenotoxic Activity of Gadoteric Acid in SH-SY5Y Cells and XIAP Interaction With Molecular Docking","authors":"Batuhan Bilgin, Mehmet Tahir Husunet, Ibrahim Halil Kenger","doi":"10.1002/jat.4884","DOIUrl":"10.1002/jat.4884","url":null,"abstract":"<div>\u0000 \u0000 <p>Gadoteric acid is a gadolinium-based contrast agent (GBCA) used to improve image quality in magnetic resonance imaging (MRI). Although it is also used in the diagnosis and prognosis of neuroblastoma, its effect on SH-SY5Y neuroblastoma cells remains unclear as a scientific gap. The aim of this study was to investigate the effects of gadoteric acid on cytogenotoxicity in SH-SY5Y neuroblastoma cells and its affinity with X-linked inhibitor of apoptosis (XIAP). After treatment of SH-SY5Y cells with gadoteric acid (0.1, 1, 10, and 100 mM), cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. After determining the IC50 value of gadoteric acid, the DNA damage effect of gadoteric acid (3.35, 6.7, 13.47, and 26.84 mM) on SH-SY5Y cells was investigated by Comet assay. Molecular docking analysis was carried out to identify the binding affinity of gadoteric acid to XIAP. Gadoteric acid (10 and 100 mM) significantly increased cytotoxicity in neuroblastoma cells (<i>p</i> < 0.0001 and <i>p</i> < 0.0001, respectively). Gadoteric acid (3.35, 6.7, 13.47, and 26.84 mM) caused a statistically significant increase in Genetic Damage Index (GDI) level in SH-SY5Y cells (<i>p</i> < 0.01, <i>p</i> < 0.05, <i>p</i> < 0.0001, and <i>p</i> < 0.001, respectively). Gadoteric acid (13.47 and 26.84 mM) also significantly increased the Damaged Cell Index (DCI) level in neuroblastoma cells (<i>p</i> < 0.01 and <i>p</i> < 0.01, respectively). The results of our study indicate that gadoteric acid used in MRI shows a cytogenotoxic effect on neuroblastoma cells and binds to XIAP with high affinity. These findings may provide insight into the use of gadoteric acid in the treatment of neuroblastoma and the molecular apoptosis mechanism of gadoteric acid.</p>\u0000 </div>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 11","pages":"2450-2457"},"PeriodicalIF":2.8,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144816753","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}
Mengjuan Pei, Yu Jin, Tao Yu, Xueyan Zhang, Wei Zhao, Min Zheng, Ying Qu, Bin Li, Ping Bin
{"title":"DNA and Chromosome Damage in BEAS-2B Cells Following Air-Liquid Interface Exposure to Whole Gasoline Engine Exhaust.","authors":"Mengjuan Pei, Yu Jin, Tao Yu, Xueyan Zhang, Wei Zhao, Min Zheng, Ying Qu, Bin Li, Ping Bin","doi":"10.1002/jat.4891","DOIUrl":"https://doi.org/10.1002/jat.4891","url":null,"abstract":"<p><p>Whole-component gasoline engine exhaust (GEE) has been classified as possibly carcinogenic to humans, where DNA and chromosome damage may play a key role. This study evaluated DNA and chromosome damage induced by GEE in human bronchial epithelial BEAS-2B cells using an air-liquid interface (ALI) exposure system. Following exposure to GEE at different dilution ratios, the cell relative viability (CRV), the percentage of DNA in the comet tail (TailDNA%), γ-H2AX protein expression, and chromosome damage for BEAS-2B cells were assessed using the Cell Counting Kit-8 (CCK-8) assay, the alkaline comet assay, Western Blotting, and cytokinesis-block micronucleus (CBMN) assay, respectively. Results showed that the relative survival rate of BEAS-2B cells decreased progressively with increasing GEE concentration (decreasing dilution ratios); specifically, a significant reduction was observed from the 1:10 dilution group onwards. TailDNA% increased significantly in all GEE-exposure groups compared to the clean air control, with a significant difference were observed starting from the 1:10 dilution group. γ-H2AX protein expression exhibited a nonsignificant trend of initial increase followed by a decrease. The cell nuclear division index (NDI) decreased significantly from the 1:5 dilution group onwards. The rates of micronuclei (MN), nucleoplasmic bridges (NPBs), and nuclear buds (NBUDs) increased significantly starting from the 1:10 dilution group, nondiluted GEE group, and 1:20 GEE group, respectively. These findings indicate that GEE exposure induces DNA and chromosome damage in BEAS-2B cells, and γ-H2AX may play a crucial role in DNA repair processes, although the specific mechanisms still require further investigation.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144816754","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":"Assessing the Sublethal Effects of Dibutyl Adipate on Unio Delicatus: Biochemical and Histopathological Insights.","authors":"İlker Şimşek, Pınar Arslan Yüce, Özgür Kuzukiran, Begüm Yurdakök-Dikmen, Ayhan Filazi, Aysel Çağlan Günal","doi":"10.1002/jat.4887","DOIUrl":"https://doi.org/10.1002/jat.4887","url":null,"abstract":"<p><p>Since phthalates, one of the plasticizers and endocrine disrupting compounds, are important chemicals that threaten ecosystem health, adipate derivatives have been developed as alternatives. However, information on the effects of adipates on aquatic organisms, which are nontarget species, is very limited. Therefore, in this study, the acute and sublethal effects of dibutyl adipate (DBA) on the freshwater mussel Unio delicatus were investigated. The 96-h lethal concentration (LC<sub>50</sub>) of DBA was determined as 1309.64 mg/L. Sublethal effects were determined by biochemical and histopathological examinations following exposure to DBA concentrations of 25 mg/L (1/50 of the LC<sub>50</sub>) and 65 mg/L (1/20 of the LC<sub>50</sub>) for 96 h and 21 days. Malondialdehyde levels in the gill tissues of mussels exposed to 25-mg/L DBA increased significantly on the 21 days. Additionally, glutathione levels in the digestive gland and gill tissues of mussels exposed to 25-mg/L DBA increased at 96 h. According to advanced oxidation protein product results, there was a significant increase in the digestive gland tissue at 21 days of exposure for both DBA concentrations, while there was a significant decrease in the gill tissue at 25-mg/L DBA at both exposure times. Although there was no significant change in the total antioxidant status of the hemolymph, the total oxidant status of the hemolymph showed a significant increase over 21 days of exposure and decreased at 96 h of exposure. Histopathological changes were observed only in the gill and digestive gland tissues after exposure to DBA. The fact that exposure to sublethal DBA concentrations caused changes in biochemical and histopathological parameters in mussels suggests that it may have adverse effects on organisms living in aquatic ecosystems.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144794580","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":"Toxicological Impacts of Arecoline and Tobacco in Oral Submucous Fibrosis: Mechanisms and Therapeutic Insights.","authors":"Devaraj Ezhilarasan, Vadivel Jayanth Kumar","doi":"10.1002/jat.4877","DOIUrl":"https://doi.org/10.1002/jat.4877","url":null,"abstract":"<p><p>Oral submucous fibrosis (OSMF) is an oral potentially malignant disorder associated with a high risk of malignant transformation, characterized by the excessive accumulation of extracellular matrix (ECM). The primary etiological factors contributing to OSMF include betel nut chewing, smoking, and tobacco use, with or without alcohol consumption. Exposure to betel nut, smokeless tobacco extracts, and cigarette smoke induces cytotoxicity in oral epithelial cells through apoptosis and oxidative stress, while simultaneously promoting fibroblast proliferation and ECM synthesis. Arecoline, a major alkaloid in betel nut, contributes to epithelial atrophy, senescence, and apoptosis. It also activates the JNK/ATF2/Jun pathway, leading to the activation of transforming growth factor (TGF)-β signaling in epithelial cells. TGF-β1 signaling, initiated by epithelial cells, activates fibroblasts in a paracrine manner, facilitating their transition to myofibroblasts and resulting in excessive ECM deposition within the OSMF microenvironment. Furthermore, arecoline stimulates fibroblast proliferation and activates the TGF-β1/SMAD signaling pathway, thereby promoting ECM synthesis. From a therapeutic perspective, intralesional administration of corticosteroids (such as dexamethasone, betamethasone, hydrocortisone, or triamcinolone) combined with hyaluronidase and antioxidants has shown improvements in mouth opening, burning sensations, and overall quality of life in OSMF patients. Additionally, herbal medicines such as curcumin and aloe vera have demonstrated efficacy, particularly in enhancing tongue protrusion and alleviating burning sensations, respectively. Lycopene and salvianolic acid B have also proven beneficial in relieving clinical symptoms and contributing to the long-term management of OSMF.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144789269","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}
Júlia Zocca Nunes de Barros, Luma Eduarda Lopes Escalante, Maria João Matos, Edson Luis Maistro
{"title":"Biosafety Evaluation of 6,7-Dihydroxy-3-(2-Nitrophenyl)Coumarin in Human Cells.","authors":"Júlia Zocca Nunes de Barros, Luma Eduarda Lopes Escalante, Maria João Matos, Edson Luis Maistro","doi":"10.1002/jat.4880","DOIUrl":"https://doi.org/10.1002/jat.4880","url":null,"abstract":"<p><p>Coumarins are considered a privileged scaffold in medicinal chemistry, as they may interact with biological macromolecules, presenting several pharmacological properties. Their potential makes them an object of study for the evaluation of their safety for humans, which is essential in the design of a potential drug. 6,7-Dihydroxy-3-(2-nitrophenyl)coumarin is a synthetic derivative with antioxidant properties, amongst other biological activities under study. The main goal of this study is to evaluate the potential cytotoxic and genotoxic effects of this molecule in peripheral blood mononuclear cells (PBMCs) and human hepatocellular carcinoma cells (HepG2/C3A). The results obtained for the cytotoxicity assays, evaluated by the resazurin assay, using concentrations between 0.1 and 50 μg/mL, showed that there is no decrease in cell viability for both cell lines. Regarding genotoxic assays, the data obtained by the comet assay and the micronucleus test, up to a concentration of 30 μg/mL, did not show significant DNA damage and/or chromosomal mutations for both cell types. Given these results, it can be concluded that 6,7-dihydroxy-3-(2-nitrophenyl)coumarin, up to a concentration of 30 μg/mL, does not present cytotoxic or genotoxic effects in human cells with and without hepatic metabolism. Considering that this family of coumarins, in general, presents their biological effect at low concentrations (mainly nanomolar range), the results obtained here encourage further studies with this molecule in drug discovery programs. 6,7-Dihydroxy-3-(2-nitrophenyl)coumarin is a new synthetic derivative with antioxidant properties, amongst other biological activities under study. The main goal of this study was to evaluate the potential cytotoxicity and genotoxicity of this molecule in human cells in vitro. Cytotoxicity assays in concentrations between 0.1 and 50 μg/mL showed no decrease in cell viability. Comet assay and the micronucleus test, up to a concentration of 30 μg/mL, did not show genetic toxicity.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144789268","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}
Kirthana Kunikullaya U, Zuzanna M Baran, Pascal Coumailleau, Laetitia Guillot, Harry W M Steinbusch, Fatima Smagulova, Thierry D Charlier
{"title":"Perinatal Exposure to the Neonicotinoid Thiacloprid Impacts Transcription of Neuroplasticity and Neuroendocrine Markers in Mice but Not in the Zebrafish Model.","authors":"Kirthana Kunikullaya U, Zuzanna M Baran, Pascal Coumailleau, Laetitia Guillot, Harry W M Steinbusch, Fatima Smagulova, Thierry D Charlier","doi":"10.1002/jat.4878","DOIUrl":"https://doi.org/10.1002/jat.4878","url":null,"abstract":"<p><p>Neonicotinoids are widely used insecticides in agriculture, aquaculture, pet care, and urban pest control. Initially developed to selectively target the insect cholinergic system, their extensive use has raised concerns about adverse effects on nontarget vertebrates. This study investigated the developmental neurotoxicity of the neonicotinoid thiacloprid using two vertebrate models: zebrafish and mice. Transgenic cyp19a1b-GFP zebrafish eleutheroembryos, which report estrogenic activity, were exposed to thiacloprid (10<sup>-6</sup>-10<sup>-8</sup> M) for 4-5 days. No significant changes were observed in GFP expression or neuroplasticity and neuroendocrine markers, suggesting a limited impact in this aquatic model. In contrast, prenatal exposure of mice to thiacloprid (0.06, 0.6, or 6 mg/kg/day from embryonic day 6.5 to 15.5) produced dose-, sex-, and region-specific alterations in brain gene expression during adolescence (postnatal day 35). At low to mid doses, markers of neurogenesis and plasticity, such as doublecortin in the amygdala, neurogenin, nestin, and PCNA in the hippocampus and cerebellum, were upregulated. However, high-dose exposure (6 mg/kg/day) led to reduced expression of these markers, including BDNF in the hypothalamus and PCNA in the hippocampus, particularly in females. These results indicate that thiacloprid, even at low doses, can subtly but significantly affect mammalian brain development. Further research is needed to assess the neurodevelopmental risks of neonicotinoids in vertebrates, including humans.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144775458","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}
Cristiane Gomes Fernandes Freire, Luana Aparecida Cunha, Mateus Andrade Stecca, Isabele Masson de Brito, Rafaella Riccio da Silva, Thiago Donizeth da Silva, Margarida Pereira Santos, Márcia Cristina Bizinotto de Assunção, Geraldo José Medeiros Fernandes, Evelise Aline Soares
{"title":"Assessment of the Effects of Cigarette Smoke on the Renal Morphology of WISTAR Rats.","authors":"Cristiane Gomes Fernandes Freire, Luana Aparecida Cunha, Mateus Andrade Stecca, Isabele Masson de Brito, Rafaella Riccio da Silva, Thiago Donizeth da Silva, Margarida Pereira Santos, Márcia Cristina Bizinotto de Assunção, Geraldo José Medeiros Fernandes, Evelise Aline Soares","doi":"10.1002/jat.4872","DOIUrl":"https://doi.org/10.1002/jat.4872","url":null,"abstract":"<p><p>Smoking is a major public health concern worldwide. The toxic components of cigarettes, such as nicotine, can cause abuse, dependence, and tissue damage. This study aimed to evaluate the effects of exposure to cigarette smoke on the renal morphology of Wistar rats. For this purpose, 12 male rats were used, divided into two groups (n = 6): CT Group (control) and CG Group (cigarette). The CG Group was exposed to smoke from six cigarettes per day. After 12 weeks, the rats were euthanized, and the kidneys were collected, weighed, and processed histologically for renal tissue analysis. Although the increase in renal weight was not statistically significant (p = 0.479), the CG Group exhibited significantly reduced values for glomerular diameter, capsular area (p < 0.0001), subcapsular area (p = 0.0045), and glomerular tuft area (p = 0.0049) compared to the CT Group. These results indicate that cigarette smoke exposure induces morphological changes in renal structure, even in the absence of significant weight alteration.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764956","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":"Oral Administration of Cadmium Chloride Induces Oxidative Stress, DNA Damage and Histopathological Changes in Rat Intestine: A Dose-Dependent Study.","authors":"Zarmin Iqbal, Aijaz Ahmed Khan, Riaz Mahmood","doi":"10.1002/jat.4879","DOIUrl":"https://doi.org/10.1002/jat.4879","url":null,"abstract":"<p><p>Cadmium (Cd) is a heavy metal that is a persistent environmental contaminant. Cd has gained global attention due to its widespread use in industries and represents an occupational hazard. Humans are exposed to Cd via the oral route throughout their lifetime, which can adversely affect their health. The present study was done to delineate the mechanism of acute toxicity of cadmium chloride (CdCl<sub>2</sub>) on rat intestine. Adult male Wistar rats were given a single oral dose of CdCl<sub>2</sub> at 30, 60, 90, and 120 mg/kg body weight. The administration of CdCl<sub>2</sub> impaired the enzymatic and non-enzymatic antioxidant defense systems, which lowered the total antioxidant capacity of intestinal cells. The oxidation of lipids, proteins, and thiol groups was significantly increased. The activities of enzymes of the brush border membrane and glucose metabolism were also altered. DNA strand scission and DNA-protein cross-linking were enhanced in CdCl<sub>2</sub>-treated rats. Histopathologic images supported the biochemical findings and showed detrimental changes in the intestine of CdCl<sub>2</sub>-treated rats. All effects were seen in a CdCl<sub>2</sub> dose-dependent manner. The results of this study strongly suggest that the toxic effects of CdCl<sub>2</sub> in rat intestine are due to the induction of oxidative stress that lowers the antioxidant defense system, leading to tissue damage.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760220","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":"Developmental-Stage-Dependent Gape Limitation in the Toxic Effect of Polystyrene Microbeads on the Water Flea, Daphnia magna.","authors":"Haruka Ito, Hitoshi Miyakawa","doi":"10.1002/jat.4875","DOIUrl":"https://doi.org/10.1002/jat.4875","url":null,"abstract":"<p><p>Complex mechanisms by which microplastics exert toxicity in natural environments are poorly understood, and their ecotoxicological assessment remains challenging due to their heterogeneous nature and physical properties. Methods for standard toxicity tests, originally developed for soluble chemicals, often fail to account for microplastic-specific behaviors such as sedimentation and variable ingestion by organisms. In this study, we used a rotator-based, semi-static exposure system to evaluate developmental-stage-specific toxicity of polystyrene microbeads of two sizes (3 μm and 30 μm) on Daphnia magna. Three exposure designs were employed: continuous exposure to single bead sizes, exposure to size mixtures, and sequential exposure aligned with developmental stages. These results demonstrated that 3-μm beads exerted stronger toxic effects in early life stages, whereas 30-μm beads had greater impacts in later stages, likely due to gape limitation and ontogenetic changes in ingestion capacity. Mixed-size exposure revealed potential additive or synergistic effects, particularly for body length. The rotator system ensured homogeneous particle suspensions and reproducible data, overcoming limitations of conventional static systems. These findings highlight the need to consider particle size heterogeneity, organismal developmental stage, and exposure method when assessing microplastic toxicity. Furthermore, our findings also suggest that chronic exposure to mixed particle sizes may better represent environmental situations and reveal stronger biological impacts than single-size exposures. By integrating particle size with organismal traits and realistic exposure dynamics, this study provides insight into the multifactorial nature of microplastic toxicity and supports the development of more ecologically relevant assessment methods.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753499","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":"Histopathological Effects of Anthropogenic Toxic Element Pollution in Freshwater Fishes in Their Natural Environments: A Global Review.","authors":"Hatice Dane","doi":"10.1002/jat.4881","DOIUrl":"https://doi.org/10.1002/jat.4881","url":null,"abstract":"<p><p>Potentially toxic element pollution from increasing anthropogenic activities poses a significant threat to freshwater ecosystems. Although many studies have investigated metal toxicity in fish exposed to various toxic elements under laboratory conditions, this review aims to evaluate the histopathological damage caused by potentially toxic element pollution in freshwater fish species within their natural habitats. A thorough literature analysis was performed by examining several scientific databases for papers published from 2011 to 2025. The main keywords used to build the search strategy included anthropogenic pollution, potentially toxic elements, freshwater fish, metal accumulation, toxicity, and histopathology. This review revealed that freshwater resources in many parts of the world are polluted with potentially toxic elements such as copper (Cu), zinc (Zn), chromium (Cr), cadmium (Cd), lead (Pb), arsenic (As), nickel (Ni), and mercury (Hg) due to various anthropogenic activities and that freshwater fish are highly sensitive to toxic element pollution in their natural habitats, and the resulting histopathological damage is often severe. The present review analyzes the alterations caused by anthropogenic toxic element pollution in the natural habitats of freshwater fish species from a histopathological perspective. It argues that the pollution status in these ecosystems should be monitored with regular research for the global continuity of freshwater resources, fish species, and, in parallel, human life.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753500","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}