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}
Pub Date : 2026-01-19DOI: 10.1016/j.etap.2026.104942
Kanghee Kim , Yooeun Chae , Yeong-Jin Kim , Seonggeun Zee , Sun-Hyun Park , Chang-Beom Park
Tire wear particles release the antioxidant N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD) and its oxidative products, notably 4-hydroxydiphenylamine (4-HDPA) and 6PPD-quinone (6PPD-Q), which pose unrecognized neurotoxic hazards to aquatic life. This study demonstrates that seven-day exposure of zebrafish larvae to environmentally relevant concentrations (30 and 300 µg/L) of these compounds leads to dose-dependent locomotor deficits, with up to a 42 % reduction in swimming speed at 300 µg/L. LC-MS/MS analysis confirmed accumulation of 6PPD, 4-HDPA, and 6PPD-Q in brain tissue, where they provoked oxidative stress, elevated reactive oxygen species, and dysregulated key antioxidant enzymes. Critically, dopaminergic dysfunction emerged as a central mechanism: downregulation of tyrosine hydroxylase (th2) and dopamine transporter (dat) expression coincided with depletion of brain dopamine and behavioral impairments. Suppression of corticotropin-releasing hormone further indicated broad neuroendocrine disruption. Despite preserved motor neuron morphology, apoptotic neuronal death increased, triggering compensatory neurotrophic and anti-apoptotic gene responses. By delineating this adverse outcome pathway, from chemical exposure and brain accumulation to oxidative injury, dopaminergic collapse, and locomotor impairment, our findings provide the mechanistic evidence of tire-derived antioxidant neurotoxicity in fish. These results underscore the urgent need to reassess 6PPD use in tire formulations, inform regulatory policies on tire wear particle emissions, and guide the design of safer alternative antioxidants to protect aquatic ecosystems.
{"title":"6PPD and its metabolites induce locomotor dysfunction in zebrafish through dopaminergic disruption with brain accumulation","authors":"Kanghee Kim , Yooeun Chae , Yeong-Jin Kim , Seonggeun Zee , Sun-Hyun Park , Chang-Beom Park","doi":"10.1016/j.etap.2026.104942","DOIUrl":"10.1016/j.etap.2026.104942","url":null,"abstract":"<div><div>Tire wear particles release the antioxidant N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD) and its oxidative products, notably 4-hydroxydiphenylamine (4-HDPA) and 6PPD-quinone (6PPD-Q), which pose unrecognized neurotoxic hazards to aquatic life. This study demonstrates that seven-day exposure of zebrafish larvae to environmentally relevant concentrations (30 and 300 µg/L) of these compounds leads to dose-dependent locomotor deficits, with up to a 42 % reduction in swimming speed at 300 µg/L. LC-MS/MS analysis confirmed accumulation of 6PPD, 4-HDPA, and 6PPD-Q in brain tissue, where they provoked oxidative stress, elevated reactive oxygen species, and dysregulated key antioxidant enzymes. Critically, dopaminergic dysfunction emerged as a central mechanism: downregulation of tyrosine hydroxylase (<em>th2</em>) and dopamine transporter (<em>dat</em>) expression coincided with depletion of brain dopamine and behavioral impairments. Suppression of corticotropin-releasing hormone further indicated broad neuroendocrine disruption. Despite preserved motor neuron morphology, apoptotic neuronal death increased, triggering compensatory neurotrophic and anti-apoptotic gene responses. By delineating this adverse outcome pathway, from chemical exposure and brain accumulation to oxidative injury, dopaminergic collapse, and locomotor impairment, our findings provide the mechanistic evidence of tire-derived antioxidant neurotoxicity in fish. These results underscore the urgent need to reassess 6PPD use in tire formulations, inform regulatory policies on tire wear particle emissions, and guide the design of safer alternative antioxidants to protect aquatic ecosystems.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"122 ","pages":"Article 104942"},"PeriodicalIF":4.2,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146014954","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}
Nanoplastic fragments (NP) are a growing concern and using dog aortic endothelial cells (CnAEOC) and fluorescence microscopy, we observed an interaction between NP and cells, demonstrating a localization at the cytoplasmic level. Furthermore, the data collected show a disruption of both cell proliferation and metabolic activity. The results also show the induction of oxidative stress. In detail, NP caused an increase in the levels of ROS production and an inhibition of enzymatic defence systems. On the contrary, there was no alteration of the non-enzymatic defence mechanism. The analysis conducted to evaluate a possible induction of autophagy, a survival mechanism implemented by cells, following exposure to NP reported the absence of autophagy involvement in the model analysed. Finally, investigations were conducted regarding the involvement of NP in gene expression processes. Both RNA-seq and RT-PCR did not highlight differentially expressed genes in treated cells.
{"title":"Toxic effects of nanoplastics on a model of dog aortic cells","authors":"Giuseppina Basini , Martina Tambassi , Simona Bussolati , Francesca Grasselli , Anna Scalori , Erika Scaltriti , Stefano Grolli , Roberto Ramoni , Fausto Quintavalla , Melissa Berni","doi":"10.1016/j.etap.2026.104940","DOIUrl":"10.1016/j.etap.2026.104940","url":null,"abstract":"<div><div>Nanoplastic fragments (NP) are a growing concern and using dog aortic endothelial cells (CnAEOC) and fluorescence microscopy, we observed an interaction between NP and cells, demonstrating a localization at the cytoplasmic level. Furthermore, the data collected show a disruption of both cell proliferation and metabolic activity. The results also show the induction of oxidative stress. In detail, NP caused an increase in the levels of ROS production and an inhibition of enzymatic defence systems. On the contrary, there was no alteration of the non-enzymatic defence mechanism. The analysis conducted to evaluate a possible induction of autophagy, a survival mechanism implemented by cells, following exposure to NP reported the absence of autophagy involvement in the model analysed. Finally, investigations were conducted regarding the involvement of NP in gene expression processes. Both RNA-seq and RT-PCR did not highlight differentially expressed genes in treated cells.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"122 ","pages":"Article 104940"},"PeriodicalIF":4.2,"publicationDate":"2026-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145995620","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 : 2026-01-15DOI: 10.1016/j.etap.2026.104939
Evren Doruk ENGIN , Ayse Basak ENGIN , Atilla ENGIN
Suppression of nocturnal circadian melatonin signaling amplitude, disruption of the host's circadian clock through diet or phase shifts, and imbalances in the gut microbiome are significant factors that increase the incidence of breast cancer. After host-derived mature microRNAs (miRNAs) are secreted from intestinal epithelial cells, they pass to the microbiota as faecal or exosomal miRNAs and modify the epigenetic profile of the microbiome. Subsequently, the profile of host miRNAs is altered by metabolites, which are derived from intestinal bacteria. Bidirectional epigenetic modulations of host and microbiota trigger the activation of oncogenic transcriptional pathways in extraintestinal tissues. However, the effect of the mutual epigenetic interactions between the gut microbiota and the host on the development of extraintestinal cancer is not clear. The aim of this review is to discuss the factors influencing bidirectional epigenetic regulation mechanisms between microbial dysbiosis and the host in breast cancer.
{"title":"Bidirectional effect of intestinal microbiome and host in circadian rhythm disruption: Environmental factors and breast cancer development","authors":"Evren Doruk ENGIN , Ayse Basak ENGIN , Atilla ENGIN","doi":"10.1016/j.etap.2026.104939","DOIUrl":"10.1016/j.etap.2026.104939","url":null,"abstract":"<div><div>Suppression of nocturnal circadian melatonin signaling amplitude, disruption of the host's circadian clock through diet or phase shifts, and imbalances in the gut microbiome are significant factors that increase the incidence of breast cancer. After host-derived mature microRNAs (miRNAs) are secreted from intestinal epithelial cells, they pass to the microbiota as faecal or exosomal miRNAs and modify the epigenetic profile of the microbiome. Subsequently, the profile of host miRNAs is altered by metabolites, which are derived from intestinal bacteria. Bidirectional epigenetic modulations of host and microbiota trigger the activation of oncogenic transcriptional pathways in extraintestinal tissues. However, the effect of the mutual epigenetic interactions between the gut microbiota and the host on the development of extraintestinal cancer is not clear. The aim of this review is to discuss the factors influencing bidirectional epigenetic regulation mechanisms between microbial dysbiosis and the host in breast cancer.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"122 ","pages":"Article 104939"},"PeriodicalIF":4.2,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994698","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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