Pub Date : 2026-01-28DOI: 10.1016/j.etap.2026.104952
Nela Pavlikova, Jan Sramek, Kamila Balusikova, Vlasta Nemcova
Permethrin, a widely used pyrethroid insecticide, has been suspected of contributing to metabolic disturbances, insulin resistance, and diabetes, but its effect on pancreatic beta cells has never been investigated. We evaluated the impact of one-week exposure to sublethal concentrations (1 μM and 10 μM) of permethrin on the function and viability of INS832/3 pancreatic beta cells. Permethrin significantly decreased glucose- and KCl-stimulated insulin secretion despite only a partial reduction in intracellular insulin levels. It also altered the expression of proteins involved in glucose metabolism, energy sensing, lipid storage and exocytosis machinery, suggesting a multifaceted impairment of cell functioning. A comparative analysis using HepG2 liver cells revealed tissue-specific responses. This is the first report showing that permethrin exposure decreases insulin secretion by pancreatic beta cells. This data can help to better evaluate the risk assessment of permethrin as a potential endocrine disruptor that may increase the risk of diabetes.
{"title":"Permethrin decreased insulin secretion and the expression of proteins linked to metabolism and exocytosis in INS832/3 pancreatic beta cells","authors":"Nela Pavlikova, Jan Sramek, Kamila Balusikova, Vlasta Nemcova","doi":"10.1016/j.etap.2026.104952","DOIUrl":"10.1016/j.etap.2026.104952","url":null,"abstract":"<div><div>Permethrin, a widely used pyrethroid insecticide, has been suspected of contributing to metabolic disturbances, insulin resistance, and diabetes, but its effect on pancreatic beta cells has never been investigated. We evaluated the impact of one-week exposure to sublethal concentrations (1 μM and 10 μM) of permethrin on the function and viability of INS832/3 pancreatic beta cells. Permethrin significantly decreased glucose- and KCl-stimulated insulin secretion despite only a partial reduction in intracellular insulin levels. It also altered the expression of proteins involved in glucose metabolism, energy sensing, lipid storage and exocytosis machinery, suggesting a multifaceted impairment of cell functioning. A comparative analysis using HepG2 liver cells revealed tissue-specific responses. This is the first report showing that permethrin exposure decreases insulin secretion by pancreatic beta cells. This data can help to better evaluate the risk assessment of permethrin as a potential endocrine disruptor that may increase the risk of diabetes.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"122 ","pages":"Article 104952"},"PeriodicalIF":4.2,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146072575","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}
Pub Date : 2026-01-27DOI: 10.1016/j.etap.2026.104950
F.J. Hernández-Fernández , J. Hernández-Fernández , L.J. Lozano , E. Iniesta-López , A. Hernández-Fernández , J. Quesada-Medina , V. Caballero , A.P. de los Ríos
The increasing interest in ionic liquids (ILs) as alternative solvents for biocatalytic and industrial applications is limited by concerns regarding their potential toxicity. In this study, we compiled one of the most comprehensive ecotoxicity datasets to date for Vibrio fischeri, Daphnia magna, and Pseudokirchneriella subcapitata. Using Partial Least Squares (PLS)-based Quantitative Structure–Activity Relationship (QSAR) models, we established predictive correlations between IL structural features and ecotoxicity. The models demonstrated high robustness and predictive power, enabling identification of key molecular descriptors driving toxicity. Results consistently indicate that longer alkyl side chains in cations, higher hydrophobicity, and aromatic ring structures are associated with increased toxicity, whereas the incorporation of heteroatoms (O, OH, CN) or non-aromatic rings reduces toxicity. Anions generally exert a lower influence compared to cations, although certain highly fluorinated species substantially increase toxicity. The comparative analysis across microorganisms highlights both shared and species-specific structural determinants. These findings provide valuable insights into IL toxicity mechanisms, particularly the role of membrane accumulation and disruption, and establish design rules for the development of safer, environmentally benign ionic liquids suitable for green chemistry and biotechnological processes.
{"title":"Comparing qsar models of ionic liquid toxicity for different microorganisms to design environmentally friendly ionic liquids and elucidate mechanisms of toxicity","authors":"F.J. Hernández-Fernández , J. Hernández-Fernández , L.J. Lozano , E. Iniesta-López , A. Hernández-Fernández , J. Quesada-Medina , V. Caballero , A.P. de los Ríos","doi":"10.1016/j.etap.2026.104950","DOIUrl":"10.1016/j.etap.2026.104950","url":null,"abstract":"<div><div>The increasing interest in ionic liquids (ILs) as alternative solvents for biocatalytic and industrial applications is limited by concerns regarding their potential toxicity. In this study, we compiled one of the most comprehensive ecotoxicity datasets to date for Vibrio fischeri, Daphnia magna, and Pseudokirchneriella subcapitata. Using Partial Least Squares (PLS)-based Quantitative Structure–Activity Relationship (QSAR) models, we established predictive correlations between IL structural features and ecotoxicity. The models demonstrated high robustness and predictive power, enabling identification of key molecular descriptors driving toxicity. Results consistently indicate that longer alkyl side chains in cations, higher hydrophobicity, and aromatic ring structures are associated with increased toxicity, whereas the incorporation of heteroatoms (O, OH, CN) or non-aromatic rings reduces toxicity. Anions generally exert a lower influence compared to cations, although certain highly fluorinated species substantially increase toxicity. The comparative analysis across microorganisms highlights both shared and species-specific structural determinants. These findings provide valuable insights into IL toxicity mechanisms, particularly the role of membrane accumulation and disruption, and establish design rules for the development of safer, environmentally benign ionic liquids suitable for green chemistry and biotechnological processes.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"122 ","pages":"Article 104950"},"PeriodicalIF":4.2,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146072576","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}
Pub Date : 2026-01-23DOI: 10.1016/j.etap.2026.104949
Manuela Cipolletti , Ilaria Campesi , Marco Pellegrini , Marco Fiocchetti , Filippo Acconcia , Maria Marino
Synthetic chemicals classified as endocrine disruptors (EDs) pose health risks by interfering with sex-steroid hormone signaling. This study evaluated bisphenol A (BPA) for its effects on ERα, ERβ, and AR expression and extranuclear signaling, including ERα phosphorylation, in human monocytes from healthy male and female donors, and assessed ten additional chemicals in ERα-positive breast cancer cell lines (MCF-7, T47D). BPA increased ERα phosphorylation in both male and female monocytes without altering receptor levels, while modulating downstream signaling in a sex-dependent manner and attenuating DHT- or E2-induced effects. The ten other chemicals similarly enhanced ERα phosphorylation, often independently of direct receptor binding. These findings indicate that ERα phosphorylation is a sensitive, early marker of ED activity across immune and epithelial cells and support its use as a receptor-proximal endpoint to complement conventional transcription-based assays in next-generation ED screening strategies.
{"title":"Exploring novel biomarkers for endocrine disruptor exposure: insights into extra-nuclear signaling pathways of estrogen and androgen receptors","authors":"Manuela Cipolletti , Ilaria Campesi , Marco Pellegrini , Marco Fiocchetti , Filippo Acconcia , Maria Marino","doi":"10.1016/j.etap.2026.104949","DOIUrl":"10.1016/j.etap.2026.104949","url":null,"abstract":"<div><div>Synthetic chemicals classified as endocrine disruptors (EDs) pose health risks by interfering with sex-steroid hormone signaling. This study evaluated bisphenol A (BPA) for its effects on ERα, ERβ, and AR expression and extranuclear signaling, including ERα phosphorylation, in human monocytes from healthy male and female donors, and assessed ten additional chemicals in ERα-positive breast cancer cell lines (MCF-7, T47D). BPA increased ERα phosphorylation in both male and female monocytes without altering receptor levels, while modulating downstream signaling in a sex-dependent manner and attenuating DHT- or E2-induced effects. The ten other chemicals similarly enhanced ERα phosphorylation, often independently of direct receptor binding. These findings indicate that ERα phosphorylation is a sensitive, early marker of ED activity across immune and epithelial cells and support its use as a receptor-proximal endpoint to complement conventional transcription-based assays in next-generation ED screening strategies.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"122 ","pages":"Article 104949"},"PeriodicalIF":4.2,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146033385","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}
Particulate matter (PM) poses risks to environmental and human health, yet its toxicity mechanisms in aquatic organisms remain unclear. This study investigated the effects of 2 PM types, a standard reference material (S-PM10, NIST, USA) and particulates from the Mae Moh Power Plant, Thailand (MMPS), on zebrafish embryo development and gene expression. Embryos were exposed to various concentrations, and mortality, hatching rates, and morphological abnormalities were assessed. S-PM10, with irregular morphology and broad particle size, induced developmental defects and reduced hatching. MMPS, characterized by uniform, spherical particles, caused higher mortality. qRT-PCR revealed that S-PM10 significantly upregulated oxidative stress (sod1, gstp2) and apoptosis (bax, casp3a) genes. In contrast, MMPS downregulated oxidative stress markers but upregulated apoptosis-related genes. These results suggest particle morphology and size influence toxicity profiles, S-PM10 triggers developmental disruption, while MMPS induces acute lethality. This study underscores the importance of particle characteristics and molecular responses in evaluating PM toxicity.
{"title":"Impact of environmental particulates on zebrafish embryo development and gene expression","authors":"Pinnakarn Techapichetvanich , Varissara Chantho , Siwapech Sillapaprayoon , Chatchai Muanprasat , Phisit Khemawoot , Wittaya Pimtong","doi":"10.1016/j.etap.2026.104948","DOIUrl":"10.1016/j.etap.2026.104948","url":null,"abstract":"<div><div>Particulate matter (PM) poses risks to environmental and human health, yet its toxicity mechanisms in aquatic organisms remain unclear. This study investigated the effects of 2 PM types, a standard reference material (S-PM10, NIST, USA) and particulates from the Mae Moh Power Plant, Thailand (MMPS), on zebrafish embryo development and gene expression. Embryos were exposed to various concentrations, and mortality, hatching rates, and morphological abnormalities were assessed. S-PM10, with irregular morphology and broad particle size, induced developmental defects and reduced hatching. MMPS, characterized by uniform, spherical particles, caused higher mortality. qRT-PCR revealed that S-PM10 significantly upregulated oxidative stress (<em>sod1</em>, <em>gstp2</em>) and apoptosis (<em>bax</em>, <em>casp3a</em>) genes. In contrast, MMPS downregulated oxidative stress markers but upregulated apoptosis-related genes. These results suggest particle morphology and size influence toxicity profiles, S-PM10 triggers developmental disruption, while MMPS induces acute lethality. This study underscores the importance of particle characteristics and molecular responses in evaluating PM toxicity.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"122 ","pages":"Article 104948"},"PeriodicalIF":4.2,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146033935","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}
Pub Date : 2026-01-21DOI: 10.1016/j.etap.2026.104941
Semra Çi̇çek , Sevda Işık
Understanding the combined effects of nickel oxide nanoparticles (NiO NPs) and minor temperature changes is urgent for assessing the possible risks to aquatic organisms under global climate change and nanoparticle-associated environmental stressors. This study investigated the cytotoxic, antioxidant, reproductive and genotoxic responses of Oncorhynchus mykiss gonadal (RTG-2) cells following exposure to NiO NPs (25–250 µg/mL) under minor temperature changes (23°C, 24°C, and 25°C) for 24 and 48 h. Our results show that the toxicity induced by cubic crystal NiO NPs (10–40 nm) was strongly modulated by both temperature and exposure time. The highest toxicity (83.49 % cell death) was observed at 100 µg/mL after 48 h at 25°C. After 48 h of exposure, NiO NP treatment led to 4.7-fold and 4.4-fold increases in sod1 gene expression at 24°C compared with 23°C and 25°C, respectively. In contrast, sod2 and gpx1a gene expressions at 24°C were 2.3-fold and 7.3-fold lower than that at 23°C, respectively. Similarly, bol gene expression was decreased by 12.4-fold and 11.4-fold at 24°C and 25°C, respectively, compared with that at 23°C. Compared with the control treatment, the NiO NP treatment increased the tail DNA percentage by 46.29 %, 42.61 % and 37.75 % compared to the control groups at 23°C, 24°C and, 25℃, respectively. These results indicate that minor environmental temperature changes can significantly alter nanoparticle toxicity by disrupting oxidative and genetic defense pathways and highlight the need for revised nanoparticle risk assessments under climate change scenarios.
{"title":"Effects of nickel oxide nanoparticles and minor temperature changes on cytotoxic, antioxidant, reproductive, and genotoxic responses in gonadal Oncorhynchus mykiss cells","authors":"Semra Çi̇çek , Sevda Işık","doi":"10.1016/j.etap.2026.104941","DOIUrl":"10.1016/j.etap.2026.104941","url":null,"abstract":"<div><div>Understanding the combined effects of nickel oxide nanoparticles (NiO NPs) and minor temperature changes is urgent for assessing the possible risks to aquatic organisms under global climate change and nanoparticle-associated environmental stressors. This study investigated the cytotoxic, antioxidant, reproductive and genotoxic responses of <em>Oncorhynchus mykiss</em> gonadal (RTG-2) cells following exposure to NiO NPs (25–250 µg/mL) under minor temperature changes (23°C, 24°C, and 25°C) for 24 and 48 h. Our results show that the toxicity induced by cubic crystal NiO NPs (10–40 nm) was strongly modulated by both temperature and exposure time. The highest toxicity (83.49 % cell death) was observed at 100 µg/mL after 48 h at 25°C. After 48 h of exposure, NiO NP treatment led to 4.7-fold and 4.4-fold increases in <em>sod1</em> gene expression at 24°C compared with 23°C and 25°C, respectively. In contrast, <em>sod2</em> and <em>gpx1a</em> gene expressions at 24°C were 2.3-fold and 7.3-fold lower than that at 23°C, respectively. Similarly, <em>bol</em> gene expression was decreased by 12.4-fold and 11.4-fold at 24°C and 25°C, respectively, compared with that at 23°C. Compared with the control treatment, the NiO NP treatment increased the tail DNA percentage by 46.29 %, 42.61 % and 37.75 % compared to the control groups at 23°C, 24°C and, 25℃, respectively. These results indicate that minor environmental temperature changes can significantly alter nanoparticle toxicity by disrupting oxidative and genetic defense pathways and highlight the need for revised nanoparticle risk assessments under climate change scenarios.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"122 ","pages":"Article 104941"},"PeriodicalIF":4.2,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146014949","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}
Pub Date : 2026-01-21DOI: 10.1016/j.etap.2026.104944
Mohamed Abdeltawab , Abdel-Hameed Ebid , Osama Ahmed , Mohamed A. Mobarez , Mahmoud Ibrahim
Linezolid-associated thrombocytopenia (LAT) limits its use in critically ill patients. This double-blind, randomized, placebo-controlled trial evaluated intravenous N-acetylcysteine (IV NAC) for LAT prevention in 250 critically ill adults receiving linezolid for ≥ 48 h. Patients received IV NAC (600 mg every 12 h) or placebo. The primary endpoint was LAT incidence (platelet count <150 × 10 ³/mm³ or >50 % reduction from baseline). NAC significantly reduced LAT incidence (16.8 % vs. 41.6 %; p < 0.001), platelet transfusions (1.6 % vs. 11.2 %; p = 0.003), and linezolid discontinuations (6.4 % vs. 32.0 %; p < 0.001). NAC delayed LAT onset (adjusted hazard ratio 0.24; p < 0.001) and accelerated platelet recovery (adjusted hazard ratio 3.88; p = 0.011), with greatest benefit in moderate-severity cases. These findings suggest IV NAC may offer a preventive benefit against LAT in critically ill patients, though multicenter validation is needed to confirm generalizability across diverse clinical settings.
Clinical Trial Registration
https://clinicaltrials.gov/study/NCT05944458. Registered on July 6, 2023.
{"title":"N-acetylcysteine reduces incidence and duration of linezolid-associated thrombocytopenia in critically ill patients: A randomized controlled trial","authors":"Mohamed Abdeltawab , Abdel-Hameed Ebid , Osama Ahmed , Mohamed A. Mobarez , Mahmoud Ibrahim","doi":"10.1016/j.etap.2026.104944","DOIUrl":"10.1016/j.etap.2026.104944","url":null,"abstract":"<div><div>Linezolid-associated thrombocytopenia (LAT) limits its use in critically ill patients. This double-blind, randomized, placebo-controlled trial evaluated intravenous N-acetylcysteine (IV NAC) for LAT prevention in 250 critically ill adults receiving linezolid for ≥ 48 h. Patients received IV NAC (600 mg every 12 h) or placebo. The primary endpoint was LAT incidence (platelet count <150 × 10 ³/mm³ or >50 % reduction from baseline). NAC significantly reduced LAT incidence (16.8 % vs. 41.6 %; p < 0.001), platelet transfusions (1.6 % vs. 11.2 %; p = 0.003), and linezolid discontinuations (6.4 % vs. 32.0 %; p < 0.001). NAC delayed LAT onset (adjusted hazard ratio 0.24; p < 0.001) and accelerated platelet recovery (adjusted hazard ratio 3.88; p = 0.011), with greatest benefit in moderate-severity cases. These findings suggest IV NAC may offer a preventive benefit against LAT in critically ill patients, though multicenter validation is needed to confirm generalizability across diverse clinical settings.</div></div><div><h3>Clinical Trial Registration</h3><div><span><span>https://clinicaltrials.gov/study/NCT05944458</span><svg><path></path></svg></span>. Registered on July 6, 2023.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"122 ","pages":"Article 104944"},"PeriodicalIF":4.2,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146033386","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}
Pub Date : 2026-01-20DOI: 10.1016/j.etap.2026.104946
Cindy C.M. Santos , Peterson E.G. Paixão , Juliana O. Meneses , Joel A.R. Dias , Amanda S. Carvalho , Hugo Leandro dos Santos , Thigna de Carvalho Batista , Patricia Severino , Eliana B. Souto , Juliana C. Cardoso , Rodrigo Y. Fujimoto
Aquaculture production is often linked to improper use of chemotherapeutic agents for pathogen control, leading to adverse effects in organisms and environment. As an alternative over these toxicological agents, in this study we propose the development of zinc oxide (ZnO) nanoparticles using ethanolic extract of red Aroeira (Schinus terebinthifolia) (EERA) and tested them against fish pathogens. Green synthesized ZnO nanoparticles had a mean hydrodynamic diameter of ca. 150 nm, and showed a broad-spectrum antibacterial activity, as well as antifungal and antiparasitic activities against Saprolegnia parasitica and Ichthyophthirius multifiliis, at the highest tested concentrations (10 and 15 mg/mL). The extract alone showed antibacterial activity against Aeromonas hydrophila, but not against Streptococcus agalactiae, suggesting a synergistic effect between EERA and ZnO nanoparticles. These findings demonstrate that green ZnO nanoparticles hold significant potential as a multifunctional antimicrobial agent for managing various pathogens in aquaculture, offering an environmentally friendly alternative to conventional chemotherapeutics.
{"title":"Red Aroeira (Schinus terebinthifolia)-based zinc oxide nanoparticles: A green approach to combat fish pathogens","authors":"Cindy C.M. Santos , Peterson E.G. Paixão , Juliana O. Meneses , Joel A.R. Dias , Amanda S. Carvalho , Hugo Leandro dos Santos , Thigna de Carvalho Batista , Patricia Severino , Eliana B. Souto , Juliana C. Cardoso , Rodrigo Y. Fujimoto","doi":"10.1016/j.etap.2026.104946","DOIUrl":"10.1016/j.etap.2026.104946","url":null,"abstract":"<div><div>Aquaculture production is often linked to improper use of chemotherapeutic agents for pathogen control, leading to adverse effects in organisms and environment. As an alternative over these toxicological agents, in this study we propose the development of zinc oxide (ZnO) nanoparticles using ethanolic extract of red Aroeira (<em>Schinus terebinthifolia</em>) (EERA) and tested them against fish pathogens. Green synthesized ZnO nanoparticles had a mean hydrodynamic diameter of ca. 150 nm, and showed a broad-spectrum antibacterial activity, as well as antifungal and antiparasitic activities against <em>Saprolegnia parasitica</em> and <em>Ichthyophthirius multifiliis</em>, at the highest tested concentrations (10 and 15 mg/mL). The extract alone showed antibacterial activity against <em>Aeromonas hydrophila</em>, but not against <em>Streptococcus agalactiae</em>, suggesting a synergistic effect between EERA and ZnO nanoparticles. These findings demonstrate that green ZnO nanoparticles hold significant potential as a multifunctional antimicrobial agent for managing various pathogens in aquaculture, offering an environmentally friendly alternative to conventional chemotherapeutics.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"122 ","pages":"Article 104946"},"PeriodicalIF":4.2,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146014952","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}
Pub Date : 2026-01-20DOI: 10.1016/j.etap.2026.104947
Júlia Robert Teixeira , Livia Alves de Macedo Tavares , Ariana Pereira da Silva , João Vitor de Macedo-Sampaio , Hugo Alexandre de Oliveira Rocha , Katia Castanho Scortecci , Bruno Fiorelini Pereira , Ana Carolina Luchiari
Ametryn (AMT) and Carbendazim (CBZ) are pesticides widely used in agricultural crops to control pests and increase food production efficiency. Despite their toxicological risks and questionable effectiveness, the real impacts of exposure to these compounds and their residues in the environment are still difficult to determine, particularly when lethal, sublethal, biochemical, and behavioral endpoints are not evaluated within the same experimental framework. This study aimed to evaluate the effects of acute exposure to AMT and CBZ in non-target organisms, using zebrafish (Danio rerio) as a model. Zebrafish embryos were exposed from 3 to 120 h post-fertilization to different concentrations of the chemicals: 0.2, 1.0, 2.0, 20, and 40 mg/L of AMT, and 0.07, 0.15, 0.3, 0.5, and 1 µg/L of CBZ (n = 20/group). Mortality, teratogenicity, cardiotoxicity, and neurotoxicity were assessed. High mortality and malformation induction were observed for both pesticides, with estimated LC₅₀ values of 1.33 mg/L for AMT and 0.02 µg/L for CBZ. Both pesticides induced increased heart rate compared to the control group. Furthermore, the pesticides reduced avoidance behavior and elevated reactive oxygen species (ROS) and apoptotic cells at concentrations below LC₅₀, evidencing their neurotoxic effects. These findings highlight the importance of integrating sublethal and neurobehavioral endpoints into ecological risk assessment of pesticide exposure.
{"title":"Neurotoxicity and teratogenicity induced by carbendazim and ametryn in zebrafish: Implications for environmental and biological health","authors":"Júlia Robert Teixeira , Livia Alves de Macedo Tavares , Ariana Pereira da Silva , João Vitor de Macedo-Sampaio , Hugo Alexandre de Oliveira Rocha , Katia Castanho Scortecci , Bruno Fiorelini Pereira , Ana Carolina Luchiari","doi":"10.1016/j.etap.2026.104947","DOIUrl":"10.1016/j.etap.2026.104947","url":null,"abstract":"<div><div>Ametryn (AMT) and Carbendazim (CBZ) are pesticides widely used in agricultural crops to control pests and increase food production efficiency. Despite their toxicological risks and questionable effectiveness, the real impacts of exposure to these compounds and their residues in the environment are still difficult to determine, particularly when lethal, sublethal, biochemical, and behavioral endpoints are not evaluated within the same experimental framework. This study aimed to evaluate the effects of acute exposure to AMT and CBZ in non-target organisms, using zebrafish (<em>Danio rerio</em>) as a model. Zebrafish embryos were exposed from 3 to 120 h post-fertilization to different concentrations of the chemicals: 0.2, 1.0, 2.0, 20, and 40 mg/L of AMT, and 0.07, 0.15, 0.3, 0.5, and 1 µg/L of CBZ (n = 20/group). Mortality, teratogenicity, cardiotoxicity, and neurotoxicity were assessed. High mortality and malformation induction were observed for both pesticides, with estimated LC₅₀ values of 1.33 mg/L for AMT and 0.02 µg/L for CBZ. Both pesticides induced increased heart rate compared to the control group. Furthermore, the pesticides reduced avoidance behavior and elevated reactive oxygen species (ROS) and apoptotic cells at concentrations below LC₅₀, evidencing their neurotoxic effects. These findings highlight the importance of integrating sublethal and neurobehavioral endpoints into ecological risk assessment of pesticide exposure.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"122 ","pages":"Article 104947"},"PeriodicalIF":4.2,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146014953","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}
Pub Date : 2026-01-20DOI: 10.1016/j.etap.2026.104945
Yubeen Kim , Jisoo Song , Seung-Min Bae , Fuller W. Bazer , Gwonhwa Song , Wooyoung Jeong , Whasun Lim
Tolylfluanid is a phenylsulfamide fungicide commonly used to manage fungal diseases in crops; however, evidence has shown its unintended toxicity in non-target organisms. To elucidate its cellular impact, we investigated how tolylfluanid affects bovine mammary epithelial (MAC-T) cells. The results revealed that exposure to tolylfluanid suppressed MAC-T cell viability, enhanced apoptotic responses, and disrupted 3D spheroid development compared with the control group. The treatment provoked excessive generation of ROS, elevated mitochondrial calcium accumulation, and triggered a reduction in mitochondrial membrane potential. These alterations were accompanied by oxidative stress–mediated mitochondrial depolarization, which was alleviated when cells were co-treated with N-acetyl-L-cysteine. Western blotting and RT-qPCR further demonstrated that tolylfluanid activated PI3K and MAPK signaling and upregulated inflammation-related genes. Additionally, real-time oxygen consumption measurements reveal mitochondrial dysfunction following tolylfluanid. Altogether, these findings indicate that tolylfluanid exerts cytotoxic and pro-oxidative effects on MAC-T cells, suggesting possible implications for milk production efficiency in cattle.
{"title":"Tolylfluanid induces mitochondrial dysfunction through excessive ROS generation and inhibits cell growth in bovine mammary epithelial cells","authors":"Yubeen Kim , Jisoo Song , Seung-Min Bae , Fuller W. Bazer , Gwonhwa Song , Wooyoung Jeong , Whasun Lim","doi":"10.1016/j.etap.2026.104945","DOIUrl":"10.1016/j.etap.2026.104945","url":null,"abstract":"<div><div>Tolylfluanid is a phenylsulfamide fungicide commonly used to manage fungal diseases in crops; however, evidence has shown its unintended toxicity in non-target organisms. To elucidate its cellular impact, we investigated how tolylfluanid affects bovine mammary epithelial (MAC-T) cells. The results revealed that exposure to tolylfluanid suppressed MAC-T cell viability, enhanced apoptotic responses, and disrupted 3D spheroid development compared with the control group. The treatment provoked excessive generation of ROS, elevated mitochondrial calcium accumulation, and triggered a reduction in mitochondrial membrane potential. These alterations were accompanied by oxidative stress–mediated mitochondrial depolarization, which was alleviated when cells were co-treated with N-acetyl-<span>L</span>-cysteine. Western blotting and RT-qPCR further demonstrated that tolylfluanid activated PI3K and MAPK signaling and upregulated inflammation-related genes. Additionally, real-time oxygen consumption measurements reveal mitochondrial dysfunction following tolylfluanid. Altogether, these findings indicate that tolylfluanid exerts cytotoxic and pro-oxidative effects on MAC-T cells, suggesting possible implications for milk production efficiency in cattle.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"122 ","pages":"Article 104945"},"PeriodicalIF":4.2,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146014956","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}
Pub Date : 2026-01-20DOI: 10.1016/j.etap.2026.104943
Rahul Kumar , Ashwin Chinala , Rama R. Gullapalli
Cadmium (Cd) is an anthropogenic toxic heavy metal pollutant with a biological half-life on the order of decades. Chronic Cd exposures through industrial sources, cigarette smoke (1° and 2°), and contaminated food and/or water sources lead to progressive bioaccumulation, particularly in the human liver and kidneys. In hepatocytes, Cd is a potent inducer of mitochondrial dysfunction and oxidative stress. Cd exposures initiate a cascade of reactive oxygen species (ROS) production, triggering redox imbalances, acute and chronic inflammation, and, in extreme exposures, cellular death. While mitochondria are well recognized as central targets of Cd toxicity, the precise mechanisms linking Cd-induced mitochondrial damage driving chronic liver and metabolic diseases remains incompletely understood. Emerging evidence implicates Cd exposure as a direct inhibitor of the mitochondrial electron transport chain (ETC) complexes and disruption of calcium homeostasis as key, converging pathways of hepatocellular injury. And yet, their specific molecular underpinnings are still unknown. This review focuses on how Cd exposures perturb mitochondrial bioenergetics, calcium signaling, and lipid signaling and metabolism within the hepatocytes specifically. Subsequently, we examine how these molecular-level alterations may contribute to the pathogenesis of chronic liver disease. In this review article, we present a cohesive framework to highlight Cd exposures as a critical (and a model) environmental heavy metal driver of chronic hepatocellular mitochondrial injury. Prolonged heavy metal exposures (such as Cd) have significant implications for long-term human hepatic health and metabolic disorders, such as metabolic (dysfunction) associated liver injury (MASLD), a key emerging pandemic of chronic human liver disease.
{"title":"Understanding molecular mechanisms driving cadmium-induced mitochondrial dysfunction in human metabolic liver disease","authors":"Rahul Kumar , Ashwin Chinala , Rama R. Gullapalli","doi":"10.1016/j.etap.2026.104943","DOIUrl":"10.1016/j.etap.2026.104943","url":null,"abstract":"<div><div>Cadmium (Cd) is an anthropogenic toxic heavy metal pollutant with a biological half-life on the order of decades. Chronic Cd exposures through industrial sources, cigarette smoke (1° and 2°), and contaminated food and/or water sources lead to progressive bioaccumulation, particularly in the human liver and kidneys. In hepatocytes, Cd is a potent inducer of mitochondrial dysfunction and oxidative stress. Cd exposures initiate a cascade of reactive oxygen species (ROS) production, triggering redox imbalances, acute and chronic inflammation, and, in extreme exposures, cellular death. While mitochondria are well recognized as central targets of Cd toxicity, the precise mechanisms linking Cd-induced mitochondrial damage driving chronic liver and metabolic diseases remains incompletely understood. Emerging evidence implicates Cd exposure as a direct inhibitor of the mitochondrial electron transport chain (ETC) complexes and disruption of calcium homeostasis as key, converging pathways of hepatocellular injury. And yet, their specific molecular underpinnings are still unknown. This review focuses on how Cd exposures perturb mitochondrial bioenergetics, calcium signaling, and lipid signaling and metabolism within the hepatocytes specifically. Subsequently, we examine how these molecular-level alterations may contribute to the pathogenesis of chronic liver disease. In this review article, we present a cohesive framework to highlight Cd exposures as a critical (and a model) environmental heavy metal driver of chronic hepatocellular mitochondrial injury. Prolonged heavy metal exposures (such as Cd) have significant implications for long-term human hepatic health and metabolic disorders, such as metabolic (dysfunction) associated liver injury (MASLD), a key emerging pandemic of chronic human liver disease.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"122 ","pages":"Article 104943"},"PeriodicalIF":4.2,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146014950","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}
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