Kilian Petitjean , Giovanna Dicara , Sébastien Bristeau , Hugo Coppens-Exandier , Laurence Amalric , Nicole Baran , Camille C. Savary , Anne Corlu , Pascal Loyer , Bernard Fromenty
{"title":"The dithiocarbamate pesticides maneb and mancozeb disturb the metabolism of lipids and xenobiotics in an in vitro model of metabolic dysfunction-associated steatotic liver disease","authors":"Kilian Petitjean , Giovanna Dicara , Sébastien Bristeau , Hugo Coppens-Exandier , Laurence Amalric , Nicole Baran , Camille C. Savary , Anne Corlu , Pascal Loyer , Bernard Fromenty","doi":"10.1016/j.etap.2025.104773","DOIUrl":"10.1016/j.etap.2025.104773","url":null,"abstract":"<div><div>Pesticides are increasingly recognized to be hepatotoxic, but less is known about their toxicity in metabolic dysfunction-associated steatotic liver disease (MASLD). Herein, differentiated HepaRG cells cultured for 2 weeks without (-FA) or with (+FA) a mixture of fatty acids were treated with different pesticides, including maneb and mancozeb, during the same period. While maneb and mancozeb did not induce neutral lipid accumulation in -FA-HepaRG cells, they worsened steatosis in +FA-HepaRG cells. MnCl<sub>2</sub> treatment reproduced these effects. Maneb or MnCl<sub>2</sub> impaired very low-density lipoprotein (VLDL) secretion and increased fatty acid uptake. Zinc supplementation restored VLDL secretion, reduced fatty acid uptake, and prevented steatosis worsening in +FA-HepaRG cells treated with mancozeb or MnCl<sub>2</sub>. Maneb, or MnCl<sub>2,</sub> also reduced the mRNA expression and activity of several cytochromes P450 in +FA- and -FA-HepaRG cells. This was associated with impaired biotransformation of diazinon. These findings could have major pathophysiological consequences in dithiocarbamate-exposed individuals with MASLD.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"118 ","pages":"Article 104773"},"PeriodicalIF":4.2,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144696973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rebeca Emanuelle da Silva Castor, Vinícius Martins, Elaine Cristina Mathias da Silva
{"title":"Impacts of flupyradifurone on the midgut and brain of the neotropical social bee Scaptotrigona postica and its behavioral effects","authors":"Rebeca Emanuelle da Silva Castor, Vinícius Martins, Elaine Cristina Mathias da Silva","doi":"10.1016/j.etap.2025.104772","DOIUrl":"10.1016/j.etap.2025.104772","url":null,"abstract":"<div><div>To reduce the damage caused by pesticides to non-target organisms, new active ingredients have been developed. Flupyradifurone, for example, was created with the proposal of being a safer alternative for the environment and non-target organisms. However, the effects of this insecticide on native bees in neotropical countries remain poorly understood, as most studies have been conducted on the <em>Apis mellifera</em> model bee. Using the species <em>Scaptotrigona postica</em>, in chronic oral exposure at an environmentally relevant concentration (4 mg/kg), we found that exposure to flupyradifurone did not interfere with bee survival. In addition, the insecticide was not able to alter the morphology of the midgut of the individuals, at least along 7 days of bioassay, but it did alter the arrangement of the Kenyon cells in the brains of the exposed bees. However, despite not having affected biomarkers at the tissue level and survival, the insecticide exposure reduced the bees' locomotion parameters, which may affect the performance of the exposed bees.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"118 ","pages":"Article 104772"},"PeriodicalIF":4.2,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144655235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Microplastic contamination in green mussels (Perna viridis Linnaeus, 1758) collected from the traditional fish markets along the East Java coast of Indonesia and the associated risk assessment","authors":"Agoes Soegianto , Trisnadi Widyaleksono Catur Putranto , Moch Affandi , Sri Wahyu Imamah , Siti Arfa Jamlean , Khairunnisak , Wildanun Mukholladun , Carolyn Melissa Payus","doi":"10.1016/j.etap.2025.104762","DOIUrl":"10.1016/j.etap.2025.104762","url":null,"abstract":"<div><div>The green mussels sold at traditional fish markets in East Java, Indonesia, are likely to be contaminated with microplastics as a result of their habitat in coastal waters, which are considerably impacted by human activities, including residential, industrial, and agricultural activities. This study investigates microplastic contamination in green mussels collected from five traditional fish markets along the East Java coast, Indonesia, and assesses the associated health risks to humans from consuming these mussels. The findings indicated that microplastics, identified as fiber and fragment types, in black and red colors, with sizes of < 100 µm and 100 - < 500 µm, are the most common in green mussels. Green mussels from the East Java coast, regardless of size, demonstrate similar amounts of microplastics. The polymer hazard index value of green mussels collected from traditional fish markets can be classified within the 860 (III = high) to 1980 (IV = very high) hazard categories. Various hazardous chemical compounds and harmful polymers that are commonly used in plastic production were detected in the tissues of green mussels through FTIR and GCMS analyses.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"118 ","pages":"Article 104762"},"PeriodicalIF":4.2,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144655234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evaluation of histological architecture, cellular apoptosis, dinitrophenyl protein and superoxide dismutase expressions in the gills of goldfish exposed to environmentally relevant pesticide mixtures: Potential mechanisms to disrupt osmoregulation","authors":"Esmirna Cantu , Md Saydur Rahman","doi":"10.1016/j.etap.2025.104761","DOIUrl":"10.1016/j.etap.2025.104761","url":null,"abstract":"<div><div>Pesticides are regularly used in agricultural production to increase crop yields and eliminate targeted pests. Unfortunately, these pesticides enter aquatic environments through surface runoff. In this study, we examined the effects of short-term exposure (one-week) to environmentally relevant pesticide mixtures (alconifen, atrazine, azinphos-methyl, isoproturon, linuron, metolachlor, pendimethalin, and tebucanazole) on gill architecture, oxidative stress biomarker, and cellular apoptosis in goldfish (<em>Carassius auratus</em>). Histological analysis revealed morphological alterations in the gills of fish exposed to both low- and high-dose pesticide mixtures. Immunohistological and real-time PCR results showed a significant upregulation of dinitrophenyl protein and superoxide dismutase mRNA expressions in the gills of fish exposed to pesticide mixtures. <em>In situ</em> TUNEL assay demonstrated a substantial increase in apoptotic nuclei in the gills of fish exposed to pesticide mixtures. Together, these results suggest that short-term exposure to environmentally relevant pesticide mixtures disrupts the morphology and cellular functions in the gills of teleost fishes.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"118 ","pages":"Article 104761"},"PeriodicalIF":4.2,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144655236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Metalloplastic interaction triggers renal oxeiptosis: Novel insights into KEAP1/PGAM5/AIFM1 pathway in snakeheaded fish Channa punctatus","authors":"Jumman Bakhasha, Vaishnavi Saxena, Neeti Arya, Pradeep Kumar, Abha Trivedi","doi":"10.1016/j.etap.2025.104760","DOIUrl":"10.1016/j.etap.2025.104760","url":null,"abstract":"<div><div>Oxeiptosis, discovered in 2018, is a ROS-triggered, caspase-independent cell death pathway studied so far only in mammals. Our study provides the first validation of oxeiptosis in an aquatic organism, expanding the understanding of oxidative stress-mediated cell death pathways in fish. <em>Channa punctatus</em> were exposed to environmentally relevant concentrations of Polyvinyl chloride microplastics (PVC-MPs) (0.5 mg/L) and copper (0.85 mg/L), both individually and in combination, for 60 days. Renal responses were evaluated through reactive oxygen species (ROS) accumulation, oxidative damage to lipids, proteins, and nucleic acids, alterations in creatinine levels, nephro-architectural deterioration, and oxeiptotic cell death. Notably, the highest copper accumulation was detected in kidneys exposed to copper-loaded PVC-MPs. Elevated ROS levels were accompanied by a decline in reduced glutathione (GSH), alongside oxidative damage markers such as heightened lipid peroxidation (LPO), protein carbonylation (PC), and 8-hydroxy-2′-deoxyguanosine (8-OHdG). Kidney dysfunction was evident from markedly increased creatinine levels, while pronounced renal architectural damage further reinforced the severity of toxicity. Molecular perturbations were more pronounced in kidneys exposed to the combined copper-PVC-MPs treatment. Transcriptional analyses indicated the upregulation of <em>keap1, pgam5,</em> and <em>aifm1</em>, with concurrent downregulation of <em>nrf2</em>, substantiating the occurrence of oxeiptosis. Additionally, Principal Component Analysis (PCA) and Pearson correlation analysis established strong associations between oxidative stress, molecular responses, and nephro-structural damage. These findings highlight that PVC-MPs act as carriers of heavy metals, amplifying oxidative stress and exacerbating renal dysfunction in aquatic organisms.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"118 ","pages":"Article 104760"},"PeriodicalIF":4.2,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144669140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The 24p3 receptor is implicated in cadmium-induced distal tubule nephrotoxicity","authors":"Ana Karen Pantaleón-Gómez , Sabino Hazael Avila-Rojas , Itzel Pamela Zavala-Guevara , Iliana Angélica Tostado-Fernández , Fanis Missirlis , Omar Emiliano Aparicio-Trejo , Belén Cuevas-López , Juan Carlos León-Contreras , Rogelio Hernández-Pando , Olivier Christophe Barbier","doi":"10.1016/j.etap.2025.104759","DOIUrl":"10.1016/j.etap.2025.104759","url":null,"abstract":"<div><div>Accumulation of toxic metal cadmium (Cd) in the kidney is traditionally associated with proximal tubule (PT) toxicity, but the potential involvement of the distal tubule (DT) remains less explored. A previous study suggested a role of the 24p3 receptor (24p3R), expressed in the DT, in mediating cadmium-induced damage, particularly when PT function was compromised. A murine model (C57BL/6 J male mice) employing gentamicin (GM) to impair PT reabsorption was used to redirect cadmium–metallothionein (CdMT) complexes toward the distal segment. Here, we used the same model, confirming that DT-specific injury was evident following CdMT administration, including epithelial cell flattening, vacuolization, enhanced catalase activity, lipid peroxidation, and apoptotic cell death. Cd exposure increased 24p3R expression in the DT, supporting its involvement in metal uptake. Coadministration of 24p3, an endogenous ligand of 24p3R, with CdMT significantly reduced tissue Cd levels by 75 % and alleviated histological and biochemical markers of injury, suggesting that 24p3 competes with CdMT for receptor binding, limiting Cd entry and its downstream toxicity. Administration of 24p3 alone did not provoke structural or molecular alterations in renal tissue. The results identify 24p3R as a relevant pathway in DT-targeted cadmium nephrotoxicity and highlight the potential of 24p3-based strategies for mitigating renal injury due to exposure to potentially toxic elements.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"118 ","pages":"Article 104759"},"PeriodicalIF":4.2,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144613326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daniel Fernandes da Costa , Maira da Silva Rodrigues , Luciana Marino Borali , Beatriz Marques de Souza , Hamid R. Habibi , Rafael Henrique Nóbrega
{"title":"Effects of bisphenol A alternatives (BPS and BPAF) on zebrafish (Danio rerio) spermatogenesis ex vivo: meiosis damage and transcriptional deregulation of genes related to spermatogenic processes and epigenetic regulation","authors":"Daniel Fernandes da Costa , Maira da Silva Rodrigues , Luciana Marino Borali , Beatriz Marques de Souza , Hamid R. Habibi , Rafael Henrique Nóbrega","doi":"10.1016/j.etap.2025.104757","DOIUrl":"10.1016/j.etap.2025.104757","url":null,"abstract":"<div><div>Environmental contaminants BPS and BPAF, emerging substitutes for BPA, are raising concerns as endocrine disruptors. This study assessed their effects on zebrafish spermatogenesis using <em>ex vivo</em> testicular explants exposed to 0.5, 5, or 50 µg/L of each compound for 7 days. Both chemicals impaired spermatogenesis by reducing meiotic (Spc<sub>p</sub>) and post-meiotic (Spt) cyst formation, with BPS showing stronger effects. Additionally, they altered the expression of marker genes related to spermatogenesis, steroidogenesis, and epigenetic regulation. Notably, <em>cyp19a1a</em> was upregulated by both, indicating estrogenic activity; however, BPS did not affect estrogen receptor expression, suggesting an indirect antiandrogenic mechanism, while BPAF modulated <em>esr1</em> and <em>esr2a</em>, indicating direct estrogenic effects. Our findings provide evidence that the dose-response for both compounds was non-monotonic. These results imply that BPS and BPAF can disrupt reproductive and molecular processes, challenging their safety as BPA substitutes and highlighting the need for further investigation and more stringent environmental regulations.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"117 ","pages":"Article 104757"},"PeriodicalIF":4.2,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144611727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jingran Yang , Ruirui Ding , Ling Qi , Haoran Bi , Jianan Li
{"title":"Exploring the mechanisms of hippocampal neurotoxicity induced by cypermethrin: Insights from integrated miRNA-seq and mRNA-seq analysis","authors":"Jingran Yang , Ruirui Ding , Ling Qi , Haoran Bi , Jianan Li","doi":"10.1016/j.etap.2025.104758","DOIUrl":"10.1016/j.etap.2025.104758","url":null,"abstract":"<div><div>Cypermethrin (CMN) is a synthetic pyrethroid insecticide known for its neurotoxic effects, particularly in the hippocampus. To investigate the underlying molecular mechanisms, we conducted integrated microRNA (miRNA) and messenger RNA (mRNA) sequencing in HT22 hippocampal cells treated with 400 μM CMN. We identified 36 differentially expressed miRNAs and 170 target mRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed significant involvement in cell adhesion, extracellular matrix organization, and signaling pathways such as phosphoinositide 3-kinase–protein kinase B signaling pathway (PI3K-Akt), mitogen-activated protein kinase (MAPK), and extracellular matrix (ECM)–receptor interaction. Using six topological algorithms, three hub genes (Col1a2, Fn1, and Pdgfrb) were finally identified. In addition, a miRNA–mRNA regulatory network was constructed, and expression patterns of key miRNAs and mRNAs were validated via reverse transcription polymerase chain reaction (RT-PCR). These findings highlight the critical role of the miRNA–mRNA regulatory network in CMN-induced neurotoxicity. The study provides valuable insights into potential therapeutic targets and preventive strategies for CMN-associated hippocampal damage.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"117 ","pages":"Article 104758"},"PeriodicalIF":4.2,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144588286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Francesco Molinari , Gianluca Antonio Franco , Francesca Inferrera , Nicla Tranchida , Antonella Iaconis , Maria Rizzo , Davide Di Paola , Giuseppe Piccione , Enrico Gugliandolo
{"title":"Environmental factors influence goat immune response to PFOS and glyphosate: Difference between grazing and stall-feeding","authors":"Francesco Molinari , Gianluca Antonio Franco , Francesca Inferrera , Nicla Tranchida , Antonella Iaconis , Maria Rizzo , Davide Di Paola , Giuseppe Piccione , Enrico Gugliandolo","doi":"10.1016/j.etap.2025.104754","DOIUrl":"10.1016/j.etap.2025.104754","url":null,"abstract":"<div><div>The aim of the present study was to investigate the interaction of EDs with both environmental and housing systems on the immune response of grazing/stall-fed goats. Chemical endocrine disruptors are reported to contaminate food chains. Some examples of ED chemicals are PFOS and glyphosate (GLY); both are reported to weaken immunity. Grazing, compared to stall feeding, results in a greater variety in diet and microorganisms’ animals are exposed to, strengthening their immune system. An ex vivo model was used: blood samples from both grazing and stall-fed goats were exposed to EDs to assess their impact on the function of immune cells and cytokine production. Outcomes indicated that goats which were fed under stall, having an immune response that was previously compromised, were more susceptible to the combined effect of PFOS and GLY, reflecting a higher rate of increase in oxidative stress. However, regarding inflammatory cytokines, both grazing and stall-fed groups reflected similar effects. It also shows how important housing systems are to modulate the impact on livestock immunity because of EDs, in the general interest of animal health and the safety of food derived therefrom, since EDs could exert risks to human health through contaminated consumable animal products. Long-term effects of EDs have to be clearly understood among livestock, and methods ought to be worked out concerning how to minimize the presence of these risks.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"117 ","pages":"Article 104754"},"PeriodicalIF":4.2,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144577415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Can crayfish serve as bioindicator of environmental impact after exposure to Bisphenol A?","authors":"Aysel Çağlan Günal , Pinar Arslan Yuce , Marilena Briglia , Caterina Faggio","doi":"10.1016/j.etap.2025.104756","DOIUrl":"10.1016/j.etap.2025.104756","url":null,"abstract":"<div><div>Bisphenol-A (BPA), is one of the industrial chemicals used mainly in the production of polycarbonates and epoxy resins, also known as endocrine disruptor and contaminant in aquatic ecosystems. Therefore, the present study aimed to determine the sublethal effects of BPA on the narrow-clawed crayfish, in terms of haemolymph parameters and histopathological changes after 24 and 96 h exposure times. The study was conducted in semi-static bioassays with 1.14 and 0.114 mg/L BPA concentrations. The total haemocyte counts significantly decreased in the 24 h exposed to BPA (<em>p</em> < 0.05). The lactate, glucose, and calcium values of haemolymph were significantly increased in the BPA-exposed groups (<em>p</em> < 0.05). The gills and the hepatopancreas tissues of the species revealed histopathological alterations at 1.14 mg/L following exposure to BPA in both exposure durations. The results of the study showed that the BPA can affect the health status of aquatic organisms via physiology and histopathology even at sublethal levels at acute exposure times.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"117 ","pages":"Article 104756"},"PeriodicalIF":4.2,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144571878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}