Environmental Toxicology最新文献

{"title":"Carcinogenic Health Risk Assessment of Benzo[a]Pyrene Bound to PM₁₀ in Adult and Children Population Through Ambient Air in Belgrade City, Serbia.","authors":"Dragana Vukelić, Bojana Petrović, Evica Antonijević Miljaković, Andrej Šoštarić, Marijana Ćurčić, Aleksandra Buha Djordjevic, Danijela Đukić-Ćosić, Biljana Antonijević, Zorica Bulat","doi":"10.1002/tox.70052","DOIUrl":"10.1002/tox.70052","url":null,"abstract":"<p><p>Particulate matter (PM) contains various components, among which heavy metals and polycyclic aromatic hydrocarbons (PAHs) are considered the main toxic component. Serbia, a middle-income country in Southeast Europe, faces PM pollution in several towns. This study aimed to assess the carcinogenic health risk of exposure to B[a]P, a representative PAH, in Belgrade for adults and children during heating and non-heating seasons, using deterministic and probabilistic approaches for the 2018-2022 period. Average PM₁₀ levels ranged between 32.6 and 45.3 μg/m³, and B[a]P levels between 1.4 and 3.7 ng/m³. The PM₁₀ annual limit (40 μg/m³) was exceeded at five of fourteen stations, while the B[a]P annual limit (1 ng/m³) was exceeded at all considered monitoring stations. Risk assessment using both approaches resulted in Total Cancer Risk (TCR) values below the USEPA safe limit (1.0E-04) for both populations and seasons. Deterministic TCR values exceeded the 95th percentile (P95) of the probabilistic risk distribution, which represents the reasonable maximum exposure level according to USEPA. The highest TCR was obtained for adults during the heating season using both deterministic (5.63E-05) and probabilistic approach (1.60E-05, P95). Our results indicate that the probabilistic approach provides a more accurate representation of overall risk, leading to better risk management decisions, while the deterministic approach is more conservative due to reliance on average parameter values. Although the carcinogenic risk of B[a]P in Belgrade was acceptable, other PM compounds and exposure pathways should be considered simultaneously to achieve a more accurate health risk assessment.</p>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":" ","pages":"1086-1096"},"PeriodicalIF":3.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13537345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147270155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diving Deeper Into Mechanisms of Acrylamide-Induced Toxicity: RNA Sequencing Reveals Transcriptomic Alteration and Retrotransposon Expression in Drosophila melanogaster.","authors":"Oluwabukola Mary Farodoye, Titilayomi Ayomide Otenaike, Daniela Moreira Mombach, Monica Medeiros Silva, Amos Olalekan Abolaji, Elgion Lucio Da Silva Loreto","doi":"10.1002/tox.70054","DOIUrl":"10.1002/tox.70054","url":null,"abstract":"<p><p>Given the inevitability of human and animal exposure to acrylamide, there is increasing concern regarding its potential health risks. While a number of molecular mechanisms have been proposed, the complexity of acrylamide toxicological pathways and interactions remains incompletely characterized. In this study, we employed a transcriptomic approach to investigate the transcriptional responses of Drosophila melanogaster following exposure to acrylamide (100 mg/kg). Our analysis identified 634 differentially expressed genes (DEGs), with 362 upregulated and 272 downregulated. Functional analysis revealed these DEGs are enriched in pathways related to reproduction, detoxification, cellular and metabolic processes, signaling, synaptic formation and organization. Notably, acrylamide exposure upregulated the expression of tau and beta-amyloid protein precursor-like genes, both implicated in Alzheimer's disease pathology. An aversive memory test further demonstrated that acrylamide impaired the short-term memory of treated flies. Additionally, acrylamide-induced toxicity altered the expression of nine long terminal repeat retrotransposons, belonging to the gypsy and pao superfamilies. By exploring the potential role of transposable element activity in acrylamide-mediated toxicity, this study provides novel insights into the molecular mechanisms underlying its effects. Collectively, these findings offer a more comprehensive understanding of the mechanisms and pathways associated with the toxic action and detoxification of acrylamide in D. melanogaster.</p>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":" ","pages":"1105-1118"},"PeriodicalIF":3.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13537343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147270125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ecotoxicological Insights From Ex Vivo Exposure of Whole Blood to PFOS and Glyphosate: Oxidative Stress and Immune Disruption.","authors":"Francesco Molinari, Gianluca Antonio Franco, Francesca Inferrera, Nicla Tranchida, Antonella Iaconis, Maria Rizzo, Giuseppe Piccione, Enrico Gugliandolo, Davide Di Paola","doi":"10.1002/tox.70053","DOIUrl":"10.1002/tox.70053","url":null,"abstract":"<p><p>This study investigated the immunomodulatory effects of PFOS and glyphosate (GLY), both individually and in combination, on the whole blood of three ruminant species (cow, goats, and sheep) exposed ex vivo to environmentally relevant concentrations. The research focused on key biomarkers of oxidative stress (MDA), inflammation (myeloperoxidase activity, nitrite production), and immune function (TNFα and IL-6 cytokine production, both at baseline and following LPS stimulation). Results indicated species-specific differences in oxidative stress response, with sheep and goats showing higher MDA levels under combined PFOS and GLY exposure. Furthermore, co-exposure exacerbated inflammatory responses (MDA activity and NO2- production) in LPS-stimulated sheep and goats. Critically, a synergistic effect of PFOS and GLY co-exposure significantly increased both TNFα and IL-6 production across all species, even without LPS stimulation, suggesting a heightened pro-inflammatory state. These findings raise concerns about the potential of these contaminants to disrupt immune homeostasis in grazing animals, impacting their health, productivity, and disease resistance, and potentially posing risks to human health through food chain contamination. The study highlights the need for further research to elucidate the underlying molecular mechanisms and assess the long-term effects of chronic exposure to these contaminants on animal health and potential human health risks.</p>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":" ","pages":"1097-1104"},"PeriodicalIF":3.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13537357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147270111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RETRACTION: The Preventive Effects of Edible Folic Acid on Cardiomyocyte Apoptosis and Survival in Early Onset Triple-transgenic Alzheimer's Disease Model Mice.","authors":"","doi":"10.1002/tox.70167","DOIUrl":"10.1002/tox.70167","url":null,"abstract":"<p><strong>Retraction: </strong>K. Lin, C. Chiu, W. Kuo, D. Ju, C. Shen, R. Chen, C. Lin, V. P. Viswanadha, J. Liu, R. S. Huang, and C. Huang, \"The Preventive Effects of Edible Folic Acid on Cardiomyocyte Apoptosis and Survival in Early Onset Triple-transgenic Alzheimer's Disease Model Mice,\" Environmental Toxicology 33, no. 1 (2017): 83-92, https://doi.org/10.1002/tox.22498. The above article, published online on 25 October 2017 in Wiley Online Library (https://wileyonlinelibrary.com), has been retracted by agreement between the journal's Editor-in-Chief, April Rodd, and Wiley Periodicals LLC. A third party reported on PubPeer [1] that bands in Figures 2, 3, and 4 appeared to have been duplicated in other articles and preprints [Chiang et al. 2016 (https://doi.org/10.3402/fnr.v60.31417); Bai et al. 2019 (https://doi.org/10.1101/823088); and Asokan et al. 2019 (https://doi.org/10.1186/s12906-019-2700-8)]. Each article describes these bands as different samples and many show additional blots that were not included in this article. Additionally, the GAPDH control bands in Figures 2 and 3 in this article also appear to have been duplicated. The retraction has been agreed to because the evidence of data duplication and manipulation fundamentally compromises the editors' confidence in the results presented in this article. The authors were informed of the retraction. Reference [1] René Aquarius, Comments on \"The preventive effects of edible folic acid on cardiomyocyte apoptosis and survival in early onset triple-transgenic Alzheimer's disease model mice,\" PubPeer, April 2026. https://pubpeer.com/publications/76A62C91CAA2ABA60C4A9E31783C55.</p>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":" ","pages":"1119"},"PeriodicalIF":3.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13537326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148618768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Embryotoxic Effects of Monosodium Methyl Arsenate (\u0000 MSMA\u0000 ) on\u0000 Gallus gallus\u0000 : Morphological and Morphometric Evidence of Developmental Disruptions","authors":"Daniel Moreira Melo, Eduarda Scalfoni Tavares, Melyssa Kmecick, Juliana Castro Monteiro Pirovani","doi":"10.1002/tox.70194","DOIUrl":"https://doi.org/10.1002/tox.70194","url":null,"abstract":"Anthropogenic activities and the large volume of compounds released into the environment are sources of contamination for plants, animals, and humans. The herbicide monosodium methyl arsenate (MSMA) ranks among the best‐selling agricultural pesticides in Brazil. It is classified as highly toxic, containing arsenic, which crosses the placenta, reaching the developing embryo. To assess the toxic effects of these chemicals, model organisms such as chicken embryos are used, as they share phylotypic features with human embryos in the early stages of development, allowing extrapolation between species. This study aimed to identify developmental alterations in chicken embryos induced by MSMA exposure after 3 and 7 days of incubation. The experiment involved three groups of fertilized eggs injected with 0.079, 0.79, and 7.9 μg mL <jats:sup>−1</jats:sup> of an MSMA solution, along with two control groups. We collected embryos to assess mortality rates, morphometric measurements, and morphological alterations. MSMA exposure was associated with embryo mortality, with a statistically significant increase in mortality observed in the MSMA II group after 7 days of incubation, and a non‐significant tendency toward higher mortality in the remaining treated groups at the same period. Seven‐day embryos exposed to MSMA exhibited significant reductions in embryo area and head, limb, and trunk length. Furthermore, MSMA exposure led to malformations in the cephalic region, neural tube, heart, optic vesicle, limbs, and beak, along with abnormal body curvature and body wall. These anomalies correspond to congenital disorders reported in humans, such as anencephaly, myelomeningocele, and skeletal malformations. These outcomes reveal the harmful effects of MSMA on chicken embryo development and suggest potential risks for human embryogenesis.","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"5 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149021681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Reference Gene Choice on Accurate Gene Expression Analysis Under Emerging Contaminant Exposure.","authors":"Kavita Kumari, Md Aftabuddin, Subir Kumar Nag, Soma Das Sarkar, Shubhadeep Ghosh, Basanta Kumar Das","doi":"10.1002/tox.70198","DOIUrl":"https://doi.org/10.1002/tox.70198","url":null,"abstract":"<p><p>Accurate interpretation of gene expression in organisms exposed to emerging contaminants (ECs) requires reliable normalization using stable reference genes. In this study, six candidate housekeeping genes (EEF1A1, GAPDH, ACTB, TBP, RAG1, and PKM) were evaluated in fish (Labeo catla) liver under exposure to chlorpyrifos, triclosan, and oxytetracycline. Expression stability was assessed using geNorm, NormFinder, BestKeeper, and the ΔC_t method, with RefFinder providing an integrated ranking. EEF1A1 consistently showed the highest stability, whereas PKM and RAG1 were the least reliable. Normalization of the xenobiotic response gene CYP1A1 with stable (EEF1A1) versus unstable (PKM, RAG1) genes revealed that inappropriate reference gene choice produced misleading expression profiles. These results highlight the critical importance of empirical reference gene validation for accurate qRT-PCR-based gene expression analysis, particularly in ecotoxicological studies involving exposure to complex mixtures of contaminants.</p>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148988455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Terrestrial Isopods as Biotic Generators of Microplastics Following Chronic Exposure to Weathered Low‐Density Polyethylene","authors":"Christopher Musgrave, Ryan S. Prosser","doi":"10.1002/tox.70195","DOIUrl":"https://doi.org/10.1002/tox.70195","url":null,"abstract":"Terrestrial detritivores such as isopods and springtails play a vital role in cycling nutrients through soil ecosystems. Microplastics (MPs, &lt; 5 mm) are increasingly recognized as contaminants of terrestrial soils, yet little is known about whether soil invertebrates themselves are impacted by consuming these plastics or if they can generate MPs from larger plastic debris. This study investigated the ability of three isopod species ( <jats:styled-content style=\"fixed-case\"> <jats:italic>Porcellio laevis</jats:italic> </jats:styled-content> , <jats:styled-content style=\"fixed-case\"> <jats:italic>Porcellio scaber</jats:italic> </jats:styled-content> , and <jats:styled-content style=\"fixed-case\"> <jats:italic>Porcellionides pruinosus</jats:italic> </jats:styled-content> ) to fragment weathered low‐density polyethylene into MPs and assessed the impact on isopod survival and growth. Weathered polyethylene fragments were provided to isopods and replaced weekly over a 28‐day exposure; MPs generated in the sand substrate were recovered by hydrogen peroxide digestion, filtration, and microscopy, while survival and growth were also monitored throughout. All three species foraged on the fragments and produced MPs throughout the experiment (min.‐max. values: <jats:styled-content style=\"fixed-case\"> <jats:italic>P. laevis</jats:italic> </jats:styled-content> = 88.3–1676.0 μm; <jats:styled-content style=\"fixed-case\"> <jats:italic>P. scaber</jats:italic> </jats:styled-content> = 82.5–940.4 μm; and <jats:styled-content style=\"fixed-case\"> <jats:italic>P pruinosus</jats:italic> </jats:styled-content> = 75.0–823.1 μm). The mean size of MPs generated differed significantly among species and was positively correlated with isopod body size. Weekly MP production did not differ significantly among species, though <jats:styled-content style=\"fixed-case\"> <jats:italic>P. scaber</jats:italic> </jats:styled-content> and <jats:styled-content style=\"fixed-case\"> <jats:italic>P. pruinosus</jats:italic> </jats:styled-content> varied significantly across weeks; total MP production over the 28 days did not differ among species. No significant effects on isopod survival or growth were observed. These findings indicate that terrestrial isopods can generate substantial quantities of MPs from macroplastic debris without apparent adverse effects on their own survival or growth, underscoring their potential role as biotic generators of secondary MPs in terrestrial ecosystems.","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"52 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148979542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kidney Risks Linked to Per- and Polyfluoroalkyl Substance Exposure.","authors":"Venice Chávez-Valencia, Francisco Alejandro Lagunas-Rangel","doi":"10.1002/tox.70197","DOIUrl":"https://doi.org/10.1002/tox.70197","url":null,"abstract":"<p><p>Per- and polyfluoroalkyl substances (PFAS) are a large and diverse class of synthetic chemicals extensively used in industrial processes and consumer products. Human exposure to PFAS is widespread and occurs through multiple pathways, including drinking water, air, diet, household dust, textiles, cosmetics, and occupational contact, particularly with aqueous film-forming foams. Due to their extreme environmental persistence, bioaccumulative properties, and broad biological activity, PFAS are now recognized as a major public health concern. The kidney is a primary target organ for PFAS toxicity, as it plays a central role in PFAS filtration, active tubular reabsorption, and long-term retention. Many PFAS are inefficiently eliminated and accumulate in renal proximal tubular cells, resulting in sustained internal exposure and heightened susceptibility to renal injury. Consistent with this biological plausibility, growing epidemiological and experimental evidence links PFAS exposure to adverse kidney outcomes, including reduced glomerular filtration rate, chronic kidney disease, and nephrolithiasis. Emerging data further suggest an association between PFAS exposure and increased risk of renal malignancies, particularly renal cell carcinoma. This narrative review synthesizes and critically evaluates current evidence on PFAS-related kidney risks, spanning functional impairment, stone formation, chronic disease progression, and cancer development. Particular emphasis is placed on the cellular and molecular mechanisms underlying PFAS-induced nephrotoxicity, including altered renal transport, mitochondrial dysfunction, metabolic dysregulation, oxidative stress, inflammation, DNA damage, and epigenetic modifications. Finally, the review discusses potential preventive and therapeutic strategies, as well as regulatory implications for mitigating PFAS-associated kidney disease.</p>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148976086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intranasal Curcumin and N-Acetyl l-Cysteine (NAC) Attenuates Dibutyl Phthalate (DBP)-Aggravated Airway Inflammation by Targeting Ferroptosis via Nrf-2/GPx4-SLC7A11","authors":"Payal Singh,&nbsp;Sneha Kumari,&nbsp;Rashmi Singh","doi":"10.1002/tox.70035","DOIUrl":"10.1002/tox.70035","url":null,"abstract":"<div>\u0000 \u0000 <p>Ferroptosis plays a significant role in the pathophysiological development of several diseases. It is an iron-dependent type of controlled cell death triggered by oxidative stress and lipid peroxidation. Nrf2, a key regulator of the antioxidant response, protects cells from ferroptosis by regulating genes involved in iron metabolism and the synthesis and breakdown of glutathione (GSH). This study was undertaken to investigate the relationship between Nrf2-mediated oxidative stress and ferroptosis in allergic asthmatic mice, particularly when the environmental toxin DBP is present. DBP disrupts iron homeostasis and causes asthma exacerbation by inducing iron accumulation and increasing hemosiderin-loaded macrophage numbers in the lungs. <i>N</i>-acetylcysteine (NAC) and curcumin antioxidant treatments significantly reduced ferroptotic damage, increased downstream targets such as GPx4, SLC7A11, and SLC40A1, and activated the Nrf2 pathway. On the other hand, ferroptosis and lung damage were exacerbated by Nrf2 suppression. In addition to elevating reactive oxygen species (ROS), nitric oxide (NO), and 8-oxoguanine (8-oxodG), DBP exposure also decreased GSH, GPx, and SOD, which led to lipid peroxidation and increased levels of malondialdehyde (MDA). These results demonstrate the therapeutic potential of Nrf2 targeting to prevent oxidative lung injury and ferroptosis in asthma triggered by DBP.</p>\u0000 </div>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"41 10","pages":"787-806"},"PeriodicalIF":3.2,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145932825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cola hispida Leaf Extract Attenuates Carbon Tetrachloride-Induced Hepato-Reno-Hematotoxicity via Antioxidant Modulation in Rats","authors":"Njideka I. Ani,&nbsp;Nnenna Ajagu,&nbsp;Kenneth O. Okolo","doi":"10.1002/tox.70049","DOIUrl":"10.1002/tox.70049","url":null,"abstract":"<div>\u0000 \u0000 <p>Carbon tetrachloride (CCl₄) induces oxidative stress, leading to liver, kidney, and hematological toxicity. <i>Cola hispida</i>, a plant with ethnomedicinal relevance, possesses bioactive compounds with potential antioxidant properties. This study investigates the protective effects of the methanolic extract of <i>C. hispida</i> (MECH) against CCl₄-induced systemic toxicity in rats. Thirty rats were randomly assigned to six groups: controls, CCl4-only, and co-treatment with MECH at doses of 100, 300, and 600 mg/kg for 21 days, as well as the MECH-only group. CCl₄ (liquid form, Sigma-Aldrich) was diluted in olive oil to 30% (v/v) and administered intraperitoneally at 10 mL/kg once weekly. CCl₄-induced organ toxicity was assessed via changes in body and organ weights, liver and kidney function markers, hematological indices, malondialdehyde (MDA), oxidative stress biomarkers [superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx)], and histopathology. The administration of CCl₄ caused a significant (<i>p</i> &lt; 0.001) increase in hepatic and renal indices [Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), urea, creatinine, sodium], oxidative stress (elevated malondialdehyde [MDA]), and hematological disturbances [significant decrease in packed cell volume (PCV), red blood cell count (RBC), hemoglobin (Hb), and increased erythrocyte sedimentation rate (ESR) and white blood cell count (WBC)]. The methanolic extract of <i>C. hispida</i> (MECH) co-administration dose-dependently reversed these alterations. Antioxidant enzymes were significantly restored, and histopathological evaluation confirmed reduced tissue damage in the MECH-treated groups. Correlation and Principal Component Analysis (PCA) revealed strong inverse relationships between oxidative stress markers and organ function parameters. MECH exhibits potent systemic protective effects against CCl₄-induced hepato-renal and hematological damage, primarily through antioxidant and anti-inflammatory mechanisms. These findings underscore the therapeutic promise of <i>C. hispida</i> in the management of oxidative stress-related multi-organ toxicity and support its ethnopharmacological use.</p>\u0000 </div>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"41 10","pages":"1041-1059"},"PeriodicalIF":3.2,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}