Gianluca Antonio Franco, Francesca Inferrera, Nicla Tranchida, Davide Di Paola, Roberta Fusco, Salvatore Cuzzocrea, Enrico Gugliandolo
{"title":"Environmental Mycotoxins and Brain Health: Protective Role of Bromelain Against Fumonisin B1 in SH-SY5Y Cells","authors":"Gianluca Antonio Franco, Francesca Inferrera, Nicla Tranchida, Davide Di Paola, Roberta Fusco, Salvatore Cuzzocrea, Enrico Gugliandolo","doi":"10.1002/tox.70059","DOIUrl":"10.1002/tox.70059","url":null,"abstract":"<p>Fumonisin B1 (FB1), a mycotoxin commonly found in contaminated food and feed, has been increasingly implicated in neurotoxicity, although its mechanisms remain poorly understood. This study investigates the neurotoxic potential of FB1 in human SH-SY5Y neuroblastoma cells, both undifferentiated and RA-differentiated, and evaluates the protective effect of bromelain, a natural proteolytic enzyme with antioxidant and anti-inflammatory properties. Cells were exposed to 50 μM FB1 for 24 h, with or without co-treatment with bromelain (10 or 50 μg/mL). FB1 significantly reduced cell viability and triggered reactive oxygen species (ROS) production, mitochondrial membrane depolarization, lipid peroxidation, inflammatory cytokine release (IL-6 and TNF-α), and apoptosis, particularly in differentiated cells. Bromelain co-treatment attenuated these effects in a dose-dependent manner, preserving mitochondrial function, reducing oxidative and inflammatory markers, and lowering apoptotic cell death. These findings emphasize the neurotoxic risk posed by FB1 and highlight bromelain as a promising multi-target protective agent. Identifying effective countermeasures against environmental neurotoxins is crucial for public health and disease prevention.</p>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"41 11","pages":"1188-1200"},"PeriodicalIF":3.2,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/tox.70059","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147282913","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}
Yongliang Zhang, Wei Hu, Nathanial Rothman, Dingyu Liu, Jihua Li, Jun Xu, Bofu Ning, Roel Vermeulen, Qing Lan, Flemming R. Cassee, George S. Downward
{"title":"Variation on Toxic and Inflammatory Potential of Coal Smoke of Different Sources From a Region With High Lung Cancer Risk","authors":"Yongliang Zhang, Wei Hu, Nathanial Rothman, Dingyu Liu, Jihua Li, Jun Xu, Bofu Ning, Roel Vermeulen, Qing Lan, Flemming R. Cassee, George S. Downward","doi":"10.1002/tox.70075","DOIUrl":"10.1002/tox.70075","url":null,"abstract":"<p>Excess lung cancer risk in Xuanwei and Fuyuan, China, has been attributed to household air pollution from use of a locally sourced smoky (bituminous) coal. However, the carcinogenic mechanisms remain unclear. Given the important role of inflammation in lung cancer development, this study compared the proinflammatory potentials of the particulate phase of smoky coal emissions with those of a locally sourced smokeless (anthracite) coal, which poses a lower lung cancer risk. A co-culture model of lung epithelial (Calu-3) and macrophage (differentiated THP-1) cells was exposed to aerosolized particulates, followed by analysis at 24 h exposure (R0) and after 24 h of recovery (R24). Cytotoxicity was minimal, with lactate dehydrogenase (LDH) release consistently under 15% of the total LDH content. Particulate exposure reduced transepithelial electric resistance (TEER) at R0, with partial recovery by R24, indicating sustained epithelial barrier damage. IL-6 release occurred at R0 in a dose-dependent manner but normalized by R24 for most samples. No significant IL-8 release was observed. The inflammatory and toxic potential (TEER reduction and IL-6/IL-8 changes) were similar across coal types and ventilation conditions. The observed potencies showed no correlation with polycyclic aromatic hydrocarbons (PAHs) content and the observed lung cancer risks of the coal samples. In summary, transient inflammation and lasting barrier damage were observed with little contrast between different coal samples. As these results do not explain the variation of lung cancer risks, further studies examining alternative cellular pathways and biological effects are needed to elucidate the mechanisms driving lung cancer in this population.</p>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"41 11","pages":"1311-1322"},"PeriodicalIF":3.2,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/tox.70075","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147381302","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}
Magali Domallain, Romain Colpaert, Xavier Moreau, Laetitia De Jong, Karim Benbrahim, Raphael Coatmeur, Valérie Pique, Maxime Robin, Pierre‐Henri Villard
{"title":"Multiscale Effects of Environmentally Relevant Mixtures Containing Two Estrogenic Endocrine Disruptors, Chlordecone and Propylparaben, in Hydra vulgaris Pallas, 1766","authors":"Magali Domallain, Romain Colpaert, Xavier Moreau, Laetitia De Jong, Karim Benbrahim, Raphael Coatmeur, Valérie Pique, Maxime Robin, Pierre‐Henri Villard","doi":"10.1002/tox.70201","DOIUrl":"https://doi.org/10.1002/tox.70201","url":null,"abstract":"This study investigates the chronic effects of chlordecone (CLD) and propylparaben (PP), two pro‐estrogenic endocrine disruptors, on <jats:italic>Hydra vulgaris</jats:italic> Pallas, 1766 using a multiscale approach over a 14‐day exposure period. Environmentally relevant concentrations of CLD (0.5, 5, 20 μg L <jats:sup>−1</jats:sup> ) and PP (0.01, 0.05, 0.40 μg L <jats:sup>−1</jats:sup> ) were tested individually and in mixtures. CLD and PP single exposures reduced the asexual reproductive rate (RHR) by 20% at intermediate CLD and high PP concentrations, whereas mixtures caused stronger declines up to 60.0% at high concentration. Severe morphological damage occurred only under high‐dose mixtures. We analyzed the expression of 17 genes covering detoxification, oxidative stress, endocrine function, regeneration, neurotransmission, proteolysis, and epigenetic regulation. Except for <jats:italic>G6pd</jats:italic> and <jats:italic>Thypedin</jats:italic> , single exposures to CLD and PP either increased or decreased gene expression. Only a limited subset of genes ( <jats:italic>Cyp17‐like</jats:italic> and <jats:italic>Cyp1a‐like</jats:italic> under CLD; <jats:italic>Cyp17‐like</jats:italic> , <jats:italic>G6pd</jats:italic> , and <jats:italic>Thypedin</jats:italic> under PP) displayed dose‐related tendencies, while most other genes showed non‐monotonic or irregular responses typical of endocrine disruptors. Mixture effects included antagonism, potentiation, and coalition, with non‐monotonic responses such as <jats:italic>Cyp17‐like</jats:italic> induction showing a 2‐fold increase at low concentration and reversal or neutralization of oxidative‐stress markers. Mixtures also increased ubiquitin in damaged hydras exposed to high‐dose mixtures and reduced global DNA methylation (up to −43%). Together, these results highlight that mixture effects diverge markedly from single‐compound responses, show no additive effects, reinforce the importance of assessing endocrine disruptors in combination, and confirm the relevance of <jats:styled-content style=\"fixed-case\"> <jats:italic>H. vulgaris</jats:italic> </jats:styled-content> as a sensitive model at environmental concentrations.","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"32 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149130610","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":"Evaluation of Hepatotoxic and Nephrotoxic Effects of Hexachlorobenzene,\u0000 DDT\u0000 , and p,p′‐\u0000 DDE\u0000 in Rats","authors":"Khuoloud Keshim,Cihan Suleyman Erdogan,Aylin Yaba,Engin Sumer,Bayram Yilmaz","doi":"10.1002/tox.70200","DOIUrl":"https://doi.org/10.1002/tox.70200","url":null,"abstract":"ABSTRACT Persistent organic pollutants such as hexachlorobenzene (HCB), dichlorodiphenyltrichloroethane (DDT), and its major metabolite p,p′‐dichlorodiphenyldichloroethylene (p,p′‐DDE) are lipophilic organochlorine pesticides that persist in the environment and bioaccumulate in tissues. We aimed to evaluate the hepatic and renal effects of subchronic low‐dose oral exposure to HCB, DDT, and p,p′‐DDE in male rats using serum biochemistry and histopathology. Thirty‐two male Sprague–Dawley rats were randomly assigned to control, HCB, DDT, and p,p′‐DDE groups ( n = 8/group). Animals received 5 mg/kg of each compound or vehicle (corn oil) by oral gavage every other day for 5 weeks. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin, blood urea nitrogen (BUN), and creatinine were measured. Liver and kidney tissues were examined histologically and injury was quantified by a semi‐quantitative histopathological H‐score. Exposure did not significantly alter ALT, AST, total bilirubin, BUN or creatinine. However, ALP activity was significantly decreased in the DDT‐ and p,p′‐DDE‐treated groups ( p < 0.05). Histopathology showed marked renal alterations in the HCB and DDT groups, including glomerular deformation, narrowed Bowman's space, and tubular disorganization, and the renal H‐score was significantly higher than control in both groups ( p < 0.001). Hepatic architecture and H‐score were similar in all groups. Low‐dose subchronic exposure to HCB and DDT was associated with quantifiable renal histopathological alterations in the absence of parallel biochemical abnormalities, which may reflect early, subclinical nephrotoxicity. DDT and p,p′‐DDE selectively reduced serum ALP activity. These findings suggest that more sensitive endpoints than serum biomarkers may be required to detect organ injury associated with organochlorine pesticide exposure.","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"17 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088373","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}