Pub Date : 2026-02-01Epub Date: 2025-11-20DOI: 10.1016/j.cbpc.2025.110398
Sodikdjon A. Kodirov
The phenotype of action potentials (AP) in mammalian dorsal root ganglion (DRG) neurons is biphasic and thereby distinct from those in the CNS and spinal cord. The sensation of pain by DRG and its prevention may occur via many types of channels, receptors, and neurotransmitters; these are at least Cav, Kv, Nav, and TRP. The Cav, Kv, and Nav channels are prevailingly involved in the excitability of DRG neurons, while the TRP family enables the mechanosensitivity. The latter are the main family of channels, and thereby the list is extensive because of the presence of many distinct α subunits among them. Also, all major receptor channels are described in DRG, but purinergic ones could be considered important because of sensitization to ATP as a neurotransmitter. This work presents a comparative and detailed synthesis of the electrophysiological properties of intact DRG and isolated neurons, with an emphasis on the K channels involved in action potential generation.
{"title":"K channels and action potential in dorsal root ganglion of diverse animals","authors":"Sodikdjon A. Kodirov","doi":"10.1016/j.cbpc.2025.110398","DOIUrl":"10.1016/j.cbpc.2025.110398","url":null,"abstract":"<div><div>The phenotype of action potentials (AP) in mammalian dorsal root ganglion (DRG) neurons is biphasic and thereby distinct from those in the CNS and spinal cord. The sensation of pain by DRG and its prevention may occur via many types of channels, receptors, and neurotransmitters; these are at least Cav, Kv, Nav, and TRP. The Cav, Kv, and Nav channels are prevailingly involved in the excitability of DRG neurons, while the TRP family enables the mechanosensitivity. The latter are the main family of channels, and thereby the list is extensive because of the presence of many distinct α subunits among them. Also, all major receptor channels are described in DRG, but purinergic ones could be considered important because of sensitization to ATP as a neurotransmitter. This work presents a comparative and detailed synthesis of the electrophysiological properties of intact DRG and isolated neurons, with an emphasis on the K channels involved in action potential generation.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"300 ","pages":"Article 110398"},"PeriodicalIF":4.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145581914","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 : 2026-01-01Epub Date: 2025-09-12DOI: 10.1016/j.cbpc.2025.110353
Qingzheng Liu , Feifei Yan , Haoran Liu , Jing Zhang , Jidong Zhang
This study investigated the toxic effects of polystyrene (PS) and polyethylene (PE) microplastics on the cardiovascular systems of zebrafish, as well as the differences in their mechanisms. Using a larval zebrafish (Danio rerio) model, we systematically evaluate the effects of the two microplastics on growth and development, oxidative stress, myocardial cell number and structure, histopathological changes, cell apoptosis, and gene expression via physiological parameter measurements, histopathological analysis, and molecular biological techniques. The experimental results showed that PS exerted a more significant inhibitory effect on body weight, whereas PE had a more marked inhibitory effect on body length. Both substances caused a dose-dependent decrease in heart rate, induced oxidative stress, aggravated myocardial damage and fibrosis and activated inflammatory responses. Additionally, PS and PE microplastics exhibit differences in their toxic mechanisms. PS enhances toxicity primarily through the adsorption capacity of its rigid benzene ring structures. While PE, due to its strong hydrophobicity, tends to accumulate more readily in myocardial tissue and exacerbate cell apoptosis via physical damage pathways. This study is the first to compare the differential mechanisms of cardiovascular toxicity between PS and PE microplastics in zebrafish, providing scientific evidence for environmental risk assessment and human health protection related to microplastics.
{"title":"Toxic effects of polystyrene and polyethylene microplastics on the zebrafish cardiovascular system and their differential mechanisms","authors":"Qingzheng Liu , Feifei Yan , Haoran Liu , Jing Zhang , Jidong Zhang","doi":"10.1016/j.cbpc.2025.110353","DOIUrl":"10.1016/j.cbpc.2025.110353","url":null,"abstract":"<div><div>This study investigated the toxic effects of polystyrene (PS) and polyethylene (PE) microplastics on the cardiovascular systems of zebrafish, as well as the differences in their mechanisms. Using a larval zebrafish (<em>Danio rerio</em>) model, we systematically evaluate the effects of the two microplastics on growth and development, oxidative stress, myocardial cell number and structure, histopathological changes, cell apoptosis, and gene expression via physiological parameter measurements, histopathological analysis, and molecular biological techniques. The experimental results showed that PS exerted a more significant inhibitory effect on body weight, whereas PE had a more marked inhibitory effect on body length. Both substances caused a dose-dependent decrease in heart rate, induced oxidative stress, aggravated myocardial damage and fibrosis and activated inflammatory responses. Additionally, PS and PE microplastics exhibit differences in their toxic mechanisms. PS enhances toxicity primarily through the adsorption capacity of its rigid benzene ring structures. While PE, due to its strong hydrophobicity, tends to accumulate more readily in myocardial tissue and exacerbate cell apoptosis via physical damage pathways. This study is the first to compare the differential mechanisms of cardiovascular toxicity between PS and PE microplastics in zebrafish, providing scientific evidence for environmental risk assessment and human health protection related to microplastics.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"299 ","pages":"Article 110353"},"PeriodicalIF":4.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063518","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 : 2026-01-01Epub Date: 2025-09-15DOI: 10.1016/j.cbpc.2025.110356
Yuexing Zhao , Weitao Liu , Jianfeng Feng , Ning Gao , Jinzheng Liu , Ruiying Shi , Aurang Zeb , Jianling Wang , Qi Wang , Chuan Yin , Xinwei Shi , Xiang Li , Yichen Ge
Tire wear particles (TWPs) are a significant source of microplastics (MPs) and N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD) in aquatic environments. However, the combined toxicity of MPs and 6PPD to aquatic organisms remains unclear. Here, we investigated the bioaccumulation of 6PPD, developmental toxicity, oxidative stress, and metabolic alterations in zebrafish larvae following single and combined exposure to polystyrene MPs (PSMPs) and 6PPD. Our results indicated that co-exposure to PSMPs and 6PPD induced synergistic toxicity in zebrafish larvae, significantly elevating levels of reactive oxygen species (ROS) and malondialdehyde (MDA), along with enhancing antioxidant enzyme activities. PSMPs did not influence the bioaccumulation of 6PPD, but increased the concentration of 6PPD quinone (6PPD-Q) in zebrafish larvae. PSMPs and 6PPD altered the metabolomic profiles of zebrafish larvae, affecting organic acids and their derivatives, amino acids and carbohydrates.
The primary distinctions between single and combined exposures were observed in organic acids (citric acid and 9-Octadecenoic acid), sugars (D-Allose, D-Arabinose, and d-Mannose), and cholesterol. These findings imply PSMPs alter the toxicity of 6PPD to zebrafish larvae, providing valuable data for assessing the potential risks of single and combined pollution of MPs and 6PPD to aquatic creatures.
{"title":"Polystyrene microplastics alter the toxicity of 6PPD to zebrafish (Danio rerio) larvae","authors":"Yuexing Zhao , Weitao Liu , Jianfeng Feng , Ning Gao , Jinzheng Liu , Ruiying Shi , Aurang Zeb , Jianling Wang , Qi Wang , Chuan Yin , Xinwei Shi , Xiang Li , Yichen Ge","doi":"10.1016/j.cbpc.2025.110356","DOIUrl":"10.1016/j.cbpc.2025.110356","url":null,"abstract":"<div><div>Tire wear particles (TWPs) are a significant source of microplastics (MPs) and <em>N</em>-(1,3-dimethylbutyl)-<em>N</em>′-phenyl-<em>p</em>-phenylenediamine (6PPD) in aquatic environments. However, the combined toxicity of MPs and 6PPD to aquatic organisms remains unclear. Here, we investigated the bioaccumulation of 6PPD, developmental toxicity, oxidative stress, and metabolic alterations in zebrafish larvae following single and combined exposure to polystyrene MPs (PSMPs) and 6PPD. Our results indicated that co-exposure to PSMPs and 6PPD induced synergistic toxicity in zebrafish larvae, significantly elevating levels of reactive oxygen species (ROS) and malondialdehyde (MDA), along with enhancing antioxidant enzyme activities. PSMPs did not influence the bioaccumulation of 6PPD, but increased the concentration of 6PPD quinone (6PPD-Q) in zebrafish larvae. PSMPs and 6PPD altered the metabolomic profiles of zebrafish larvae, affecting organic acids and their derivatives, amino acids and carbohydrates.</div><div>The primary distinctions between single and combined exposures were observed in organic acids (citric acid and 9-Octadecenoic acid), sugars (D-Allose, D-Arabinose, and d-Mannose), and cholesterol. These findings imply PSMPs alter the toxicity of 6PPD to zebrafish larvae, providing valuable data for assessing the potential risks of single and combined pollution of MPs and 6PPD to aquatic creatures.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"299 ","pages":"Article 110356"},"PeriodicalIF":4.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074613","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 : 2026-01-01Epub Date: 2025-09-13DOI: 10.1016/j.cbpc.2025.110355
Sihan Hou , Daoyuan Qin , Daoxi Lei , Qin Wang
Octocrylene (OC), a prevalent ultraviolet (UV) filter in sunscreens, is frequently detected in soils, sediments, aquatic systems, and food chains, making it an emerging contaminant. Although evidence suggests OC impairs zebrafish larval development, its neurotoxic effects remain incompletely understood. In this study, zebrafish embryos were exposed to OC (0–30 μM) to assess impacts on early neurodevelopment. The results showed that exposure to 30 μM OC reduced the hatching rate of zebrafish and decreased their heart rate at 48 hpf. OC concentrations above 10 μM increased the body length of zebrafish larvae. Moreover, OC exposure significantly reduced various types of neural cells, including neural stem cells, neural progenitor cells, neurons, and glial cells, and led to behavioral abnormalities. Mechanistically, transcriptomic profiling revealed that the differentially expressed genes were mainly enriched in the process of activating apoptosis. Concentration-dependent increases in acridine orange (AO) and reactive oxygen species (ROS) staining confirmed apoptosis in brain tissues. Further analysis suggested that OC-induced neurotoxicity may be mediated by dysregulation of the MDM2-p53 signaling axis. These findings elucidate previously unrecognized mechanisms of OC neurotoxicity, providing critical insights for environmental risk assessment of UV filters.
{"title":"Morphological, behavioral, and molecular neurotoxicity of octocrylene in zebrafish larvae","authors":"Sihan Hou , Daoyuan Qin , Daoxi Lei , Qin Wang","doi":"10.1016/j.cbpc.2025.110355","DOIUrl":"10.1016/j.cbpc.2025.110355","url":null,"abstract":"<div><div>Octocrylene (OC), a prevalent ultraviolet (UV) filter in sunscreens, is frequently detected in soils, sediments, aquatic systems, and food chains, making it an emerging contaminant. Although evidence suggests OC impairs zebrafish larval development, its neurotoxic effects remain incompletely understood. In this study, zebrafish embryos were exposed to OC (0–30 μM) to assess impacts on early neurodevelopment. The results showed that exposure to 30 μM OC reduced the hatching rate of zebrafish and decreased their heart rate at 48 hpf. OC concentrations above 10 μM increased the body length of zebrafish larvae. Moreover, OC exposure significantly reduced various types of neural cells, including neural stem cells, neural progenitor cells, neurons, and glial cells, and led to behavioral abnormalities. Mechanistically, transcriptomic profiling revealed that the differentially expressed genes were mainly enriched in the process of activating apoptosis. Concentration-dependent increases in acridine orange (AO) and reactive oxygen species (ROS) staining confirmed apoptosis in brain tissues. Further analysis suggested that OC-induced neurotoxicity may be mediated by dysregulation of the MDM2-p53 signaling axis. These findings elucidate previously unrecognized mechanisms of OC neurotoxicity, providing critical insights for environmental risk assessment of UV filters.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"299 ","pages":"Article 110355"},"PeriodicalIF":4.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069229","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 : 2026-01-01Epub Date: 2025-10-10DOI: 10.1016/j.cbpc.2025.110368
Bence Ivánovics , Gyöngyi Gazsi , Zoltán K. Varga , Ádám Staszny , Eszter Váradi , Zsófia Varga , András Ács , Márta Tóth , Apolka Domokos , Márta Reining , Erna Vásárhelyi , Szilárd Póliska , Róbert Kovács , Ferenc Baska , Zoltán Filep , Attila Bácsi , Julianna Kobolák , Béla Urbányi , István Szabó , Tamás Müller , Zsolt Czimmerer
The emergence and spread of vector-borne diseases necessitate the increased use of insecticides, such as carbamates, raising concerns about their potential toxicological risks to non-target organisms, including humans. Bendiocarb, frequently applied in indoor spraying operations and detected in maternal and fetal circulation, warrants particular attention for its developmental toxicity. This study aimed to assess transcriptional and phenotypic effects of sublethal bendiocarb exposure at concentrations of 0.035, 0.2, 0.4, 0.75, and 1.5 mg/L, using zebrafish embryos, a vertebrate model for developmental toxicity testing. Our analyses revealed acetylcholinesterase inhibition-associated morphological and behavioral abnormalities, including reduced locomotor activity in response to both visual and tactile stimuli, as well as impaired non-associative learning. Transcriptomic analysis indicated activation of muscle, immune, and metabolic pathways, while neurodevelopmental, phototransduction, and cell proliferation processes were suppressed. Consistent with these molecular findings, structural damage was observed in the retina, skeletal muscle, and notochord. Furthermore, bendiocarb exposure disrupted neutrophil granulocyte distribution and impaired inflammatory responses. Altogether, our results provide new insights into the embryotoxic effects of bendiocarb, highlighting its potential to disrupt early vertebrate development. These findings provide mechanistic insight that may support more informed evaluations of potential public health risks associated with developmental exposure to carbamates.
{"title":"Carbamate insecticide bendiocarb induces complex embryotoxic effects, including morphological, behavioral, transcriptional, and immunological alterations in zebrafish","authors":"Bence Ivánovics , Gyöngyi Gazsi , Zoltán K. Varga , Ádám Staszny , Eszter Váradi , Zsófia Varga , András Ács , Márta Tóth , Apolka Domokos , Márta Reining , Erna Vásárhelyi , Szilárd Póliska , Róbert Kovács , Ferenc Baska , Zoltán Filep , Attila Bácsi , Julianna Kobolák , Béla Urbányi , István Szabó , Tamás Müller , Zsolt Czimmerer","doi":"10.1016/j.cbpc.2025.110368","DOIUrl":"10.1016/j.cbpc.2025.110368","url":null,"abstract":"<div><div>The emergence and spread of vector-borne diseases necessitate the increased use of insecticides, such as carbamates, raising concerns about their potential toxicological risks to non-target organisms, including humans. Bendiocarb, frequently applied in indoor spraying operations and detected in maternal and fetal circulation, warrants particular attention for its developmental toxicity. This study aimed to assess transcriptional and phenotypic effects of sublethal bendiocarb exposure at concentrations of 0.035, 0.2, 0.4, 0.75, and 1.5 mg/L, using zebrafish embryos, a vertebrate model for developmental toxicity testing. Our analyses revealed acetylcholinesterase inhibition-associated morphological and behavioral abnormalities, including reduced locomotor activity in response to both visual and tactile stimuli, as well as impaired non-associative learning. Transcriptomic analysis indicated activation of muscle, immune, and metabolic pathways, while neurodevelopmental, phototransduction, and cell proliferation processes were suppressed. Consistent with these molecular findings, structural damage was observed in the retina, skeletal muscle, and notochord. Furthermore, bendiocarb exposure disrupted neutrophil granulocyte distribution and impaired inflammatory responses. Altogether, our results provide new insights into the embryotoxic effects of bendiocarb, highlighting its potential to disrupt early vertebrate development. These findings provide mechanistic insight that may support more informed evaluations of potential public health risks associated with developmental exposure to carbamates.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"299 ","pages":"Article 110368"},"PeriodicalIF":4.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274062","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 : 2026-01-01Epub Date: 2025-09-23DOI: 10.1016/j.cbpc.2025.110365
Yue Li , Zihao Jiang , Zhuoshuo Zhou , Naitian Zhang , Ximing Cui , Xiaoyan Yu , Yanli Zhao , Zhong Wang , Jinlian Li , Dongmei Wu
Atractylenolides (I, II, and III), active sesquiterpene lactones from Atractylodes macrocephala Koidz, exhibit diverse pharmacological activities but have been reported to impair drug-metabolizing enzymes and hepatocellular function. However, a comprehensive safety assessment of these compounds remains lacking. In this study, we investigated the developmental toxicity profile of Atractylenolides (I, II, and III) in zebrafish embryos, with a particular focus on hepatotoxicity and its underlying mechanisms. Exposure to Atractylenolides (I, II, and III) resulted in concentration-dependent mortality, with 96-h median lethal concentrations (LC₅₀) of 81.64 μM, 138.40 μM, and 151.90 μM, respectively. Atractylenolides (I, II) induced multiple developmental abnormalities, among which Atractylenolide-I uniquely led to neuronal developmental arrest and diminished locomotor activity. Importantly, Atractylenolides (I, II) exhibited marked hepatotoxicity, evidenced by liver shrinkage, reduced liver-specific fluorescence intensity, and elevated levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). In contrast, exposure to Atractylenolide-III did not induce significant toxic effects. Network toxicology analysis revealed that cytochrome P450 (CYP450) metabolism and apoptosis were closely associated with Atractylenolides (I, II) induced hepatotoxicity. qRT-PCR analysis revealed that Atractylenolides (I, II) suppressed mRNA expression of key drug-metabolizing genes, including cyp3c1 and cyp3a65. Simultaneously, Atractylenolides (I, II) downregulated genes associated with cell proliferation (top2α, uhrf1). Co-treatment with the hepatoprotective agent silybin partially reversed the liver injury and the alterations in drug metabolism gene expression induced by Atractylenolides (I, II). Collectively, our results provide important insights into the safety evaluation of Atractylenolides (I, II, and III).
{"title":"Differential toxic phenotypes and liver injury induced by Atractylenolides (I, II, and III): Insights from zebrafish (Danio rerio) models and network toxicology","authors":"Yue Li , Zihao Jiang , Zhuoshuo Zhou , Naitian Zhang , Ximing Cui , Xiaoyan Yu , Yanli Zhao , Zhong Wang , Jinlian Li , Dongmei Wu","doi":"10.1016/j.cbpc.2025.110365","DOIUrl":"10.1016/j.cbpc.2025.110365","url":null,"abstract":"<div><div>Atractylenolides (I, II, and III), active sesquiterpene lactones from <em>Atractylodes macrocephala</em> Koidz, exhibit diverse pharmacological activities but have been reported to impair drug-metabolizing enzymes and hepatocellular function. However, a comprehensive safety assessment of these compounds remains lacking. In this study, we investigated the developmental toxicity profile of Atractylenolides (I, II, and III) in zebrafish embryos, with a particular focus on hepatotoxicity and its underlying mechanisms. Exposure to Atractylenolides (I, II, and III) resulted in concentration-dependent mortality, with 96-h median lethal concentrations (LC₅₀) of 81.64 μM, 138.40 μM, and 151.90 μM, respectively. Atractylenolides (I, II) induced multiple developmental abnormalities, among which Atractylenolide-I uniquely led to neuronal developmental arrest and diminished locomotor activity. Importantly, Atractylenolides (I, II) exhibited marked hepatotoxicity, evidenced by liver shrinkage, reduced liver-specific fluorescence intensity, and elevated levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). In contrast, exposure to Atractylenolide-III did not induce significant toxic effects. Network toxicology analysis revealed that cytochrome P450 (CYP450) metabolism and apoptosis were closely associated with Atractylenolides (I, II) induced hepatotoxicity. qRT-PCR analysis revealed that Atractylenolides (I, II) suppressed mRNA expression of key drug-metabolizing genes, including <em>cyp3c1</em> and <em>cyp3a65</em>. Simultaneously, Atractylenolides (I, II) downregulated genes associated with cell proliferation (<em>top2α</em>, <em>uhrf1</em>). Co-treatment with the hepatoprotective agent silybin partially reversed the liver injury and the alterations in drug metabolism gene expression induced by Atractylenolides (I, II). Collectively, our results provide important insights into the safety evaluation of Atractylenolides (I, II, and III).</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"299 ","pages":"Article 110365"},"PeriodicalIF":4.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148195","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 : 2026-01-01Epub Date: 2025-10-11DOI: 10.1016/j.cbpc.2025.110371
Shunyan Yu , Jing Gao , Yongpan Wang , Hao Ji , Weiqiang Huang
Dibutyl phthalate (DBP), a ubiquitous environmental contaminant, has been shown to induce developmental toxicity and thyroid hormone disruption in aquatic organisms. In this study, we evaluated the protective effects of the natural astaxanthin (AST) against DBP-induced toxicity in early-life stage zebrafish. Exposure to DBP (0.1–1 mg/L) significantly impaired embryonic development, reduced body length and weight, and disrupted thyroid hormone homeostasis by decreasing T4 and increasing T3 levels. These effects were accompanied by oxidative stress, inflammation, and dysregulated expression of key genes along the hypothalamic-pituitary-thyroid (HPT) axis, including dio2, tg, crhβ, and tsh. AST supplementation dose-dependently alleviated these developmental and thyroid hormone disruption, restored redox balance and anti-inflammatory responses, and normalized HPT axis gene expression. Molecular docking identified strong binding affinities between AST and core regulatory targets (HSP90AB1, HIF1A, MTOR, NFKB1), demonstrating its multi-target mechanism involving oxidative stress mitigation, metabolic regulation, and immune modulation. These findings provide new insight into AST's protective role against endocrine-disrupting pollutants and suggest its potential application in aquatic toxicology and human health.
{"title":"Astaxanthin mitigates dibutyl phthalate-induced thyroid hormone disruption in zebrafish larvae via multi-target regulation","authors":"Shunyan Yu , Jing Gao , Yongpan Wang , Hao Ji , Weiqiang Huang","doi":"10.1016/j.cbpc.2025.110371","DOIUrl":"10.1016/j.cbpc.2025.110371","url":null,"abstract":"<div><div>Dibutyl phthalate (DBP), a ubiquitous environmental contaminant, has been shown to induce developmental toxicity and thyroid hormone disruption in aquatic organisms. In this study, we evaluated the protective effects of the natural astaxanthin (AST) against DBP-induced toxicity in early-life stage zebrafish. Exposure to DBP (0.1–1 mg/L) significantly impaired embryonic development, reduced body length and weight, and disrupted thyroid hormone homeostasis by decreasing T4 and increasing T3 levels. These effects were accompanied by oxidative stress, inflammation, and dysregulated expression of key genes along the hypothalamic-pituitary-thyroid (HPT) axis, including <em>dio2</em>, <em>tg</em>, <em>crhβ</em>, and <em>tsh</em>. AST supplementation dose-dependently alleviated these developmental and thyroid hormone disruption, restored redox balance and anti-inflammatory responses, and normalized HPT axis gene expression. Molecular docking identified strong binding affinities between AST and core regulatory targets (HSP90AB1, HIF1A, MTOR, NFKB1), demonstrating its multi-target mechanism involving oxidative stress mitigation, metabolic regulation, and immune modulation. These findings provide new insight into AST's protective role against endocrine-disrupting pollutants and suggest its potential application in aquatic toxicology and human health.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"299 ","pages":"Article 110371"},"PeriodicalIF":4.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285690","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 : 2026-01-01Epub Date: 2025-10-14DOI: 10.1016/j.cbpc.2025.110372
Bi-Xia Huang , Tao Zhang , Qing-Bin Dong , Peng-Xing Lin , Yi Zhou , Xin-Shuo Chen
Iron oxide nanoparticles (IONPs) are widely applied in biomedicine and industry, yet their impact on early nervous system formation is poorly understood. Here, we assessed IONP toxicity using cultured chick embryo fibroblasts, fertilized chicken eggs, and zebrafish embryos. In vitro exposure reduced fibroblast viability, elevated lipid peroxidation, and boosted reactive oxygen species levels. The injection of IONPs in chick embryo caused growth delays, smaller brain size, neuroepithelial thickening, and marked loss of neural stem and progenitor cells. At the molecular level, IONPs reduced PI3K and mTOR activity, increased apoptotic markers, and induced ferroptosis hallmarks, including mitochondrial membrane potential loss, ATP depletion, elevated mitochondrial ROS, and downregulation of xCT and GPX4. In zebrafish, IONPs triggered early developmental defects, microcephaly, and yolk malabsorption, alongside redox imbalance and dysregulation of ferroptosis-related genes. Together, these data show that IONPs impair neural proliferation, promote multiple forms of cell death, and disrupt redox equilibrium through ferroptotic mechanisms, highlighting the need for careful safety evaluation before their widespread use.
{"title":"Neurodevelopmental toxicity induced by iron oxide nanoparticles: Insights from chick and zebrafish embryonic models","authors":"Bi-Xia Huang , Tao Zhang , Qing-Bin Dong , Peng-Xing Lin , Yi Zhou , Xin-Shuo Chen","doi":"10.1016/j.cbpc.2025.110372","DOIUrl":"10.1016/j.cbpc.2025.110372","url":null,"abstract":"<div><div>Iron oxide nanoparticles (IONPs) are widely applied in biomedicine and industry, yet their impact on early nervous system formation is poorly understood. Here, we assessed IONP toxicity using cultured chick embryo fibroblasts, fertilized chicken eggs, and zebrafish embryos. In vitro exposure reduced fibroblast viability, elevated lipid peroxidation, and boosted reactive oxygen species levels. The injection of IONPs in chick embryo caused growth delays, smaller brain size, neuroepithelial thickening, and marked loss of neural stem and progenitor cells. At the molecular level, IONPs reduced PI3K and mTOR activity, increased apoptotic markers, and induced ferroptosis hallmarks, including mitochondrial membrane potential loss, ATP depletion, elevated mitochondrial ROS, and downregulation of xCT and GPX4. In zebrafish, IONPs triggered early developmental defects, microcephaly, and yolk malabsorption, alongside redox imbalance and dysregulation of ferroptosis-related genes. Together, these data show that IONPs impair neural proliferation, promote multiple forms of cell death, and disrupt redox equilibrium through ferroptotic mechanisms, highlighting the need for careful safety evaluation before their widespread use.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"299 ","pages":"Article 110372"},"PeriodicalIF":4.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145298873","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 : 2026-01-01Epub Date: 2025-09-13DOI: 10.1016/j.cbpc.2025.110352
Hongming Tang , Juan Liu , Dong Sheng , Xu Ren , Qinghua Yu , Zhixin Guo , Yunpeng Wu , Yuxiao Liu , Yuehan Xiao , Wei Wang , Shigen Ye , Weijia Zhou
Isobavachalcone (IBC), a bioactive flavonoid derived from Psoralea corylifolia, exhibits potent anti-ciliate activity, but its underlying mechanism remains unclear. Utilizing Tetrahymena thermophila as a model organism, we demonstrated that IBC induces dose-dependent mortality (12 h-IC50: 1.39 mg/L) and inhibits growth. Mechanistically, IBC triggers oxidative stress by elevating reactive oxygen species (ROS) and disrupting antioxidant enzymes, including superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione (GSH). This disruption leads to membrane damage, as evidenced by lactate dehydrogenase (LDH) leakage and ATPase inhibition, as well as mitochondrial dysfunction. Microscopic examination and staining confirmed that cell death occurs via necrotic cell death rather than apoptosis. Transcriptome analysis revealed key pathways, including peroxisome-mediated oxidation, glutathione metabolism, and ATP-binding cassette (ABC) transporters, further supporting the role of IBC in oxidative and structural disruption. These findings elucidate the anti-ciliate mechanism of IBC, providing valuable insights for developing targeted anti-parasitic agents.
{"title":"Inhibitory effects of isobavachalcone against Tetrahymena thermophila: Mechanistic insights","authors":"Hongming Tang , Juan Liu , Dong Sheng , Xu Ren , Qinghua Yu , Zhixin Guo , Yunpeng Wu , Yuxiao Liu , Yuehan Xiao , Wei Wang , Shigen Ye , Weijia Zhou","doi":"10.1016/j.cbpc.2025.110352","DOIUrl":"10.1016/j.cbpc.2025.110352","url":null,"abstract":"<div><div>Isobavachalcone (IBC), a bioactive flavonoid derived from <em>Psoralea corylifolia</em>, exhibits potent anti-ciliate activity, but its underlying mechanism remains unclear. Utilizing <em>Tetrahymena thermophila</em> as a model organism, we demonstrated that IBC induces dose-dependent mortality (12 h-IC<sub>50</sub>: 1.39 mg/L) and inhibits growth. Mechanistically, IBC triggers oxidative stress by elevating reactive oxygen species (ROS) and disrupting antioxidant enzymes, including superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione (GSH). This disruption leads to membrane damage, as evidenced by lactate dehydrogenase (LDH) leakage and ATPase inhibition, as well as mitochondrial dysfunction. Microscopic examination and staining confirmed that cell death occurs via necrotic cell death rather than apoptosis. Transcriptome analysis revealed key pathways, including peroxisome-mediated oxidation, glutathione metabolism, and ATP-binding cassette (ABC) transporters, further supporting the role of IBC in oxidative and structural disruption. These findings elucidate the anti-ciliate mechanism of IBC, providing valuable insights for developing targeted anti-parasitic agents.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"299 ","pages":"Article 110352"},"PeriodicalIF":4.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069283","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 : 2026-01-01Epub Date: 2025-09-06DOI: 10.1016/j.cbpc.2025.110348
Kanchaka Senarath Pathirajage , Rosemaria Serradimigni , Copeland R. Johnson , Sunil Sharma , Christopher Chouinard , Subham Dasgupta
Tetrabromobisphenol A (TBBPA), a widely used flame retardant in textiles and electronics, poses toxicological risks through both environmental and indoor exposures. Biomonitoring studies have detected significant TBBPA levels in prenatal environments, including cord blood, raising concerns about developmental impacts. Using zebrafish as a model, this study addresses critical gaps in understanding how developmental TBBPA exposures perturb regulatory pathways that govern dorsoventral patterning. Embryos were exposed at 0.75- or 6-h post-fertilization (hpf) and phenotyped at 24 hpf, with tissue uptake quantified by LC-MS. At 24 hpf, embryos exhibited concentration-dependent ventralization characterized by loss of dorsal structures. Whole-mount immunohistochemistry revealed concentration-dependent alterations in dorsoventral, cell adhesion, and germ layer markers, indicating disruptions in cell migration and germ layer integrity. At later stages, even nontoxic exposures led to craniofacial and hematopoietic defects, linking early molecular perturbations to downstream developmental abnormalities. Although the phenotypes strongly resembled BMP pathway overactivation, co-exposure with the BMP inhibitor dorsomorphin failed to rescue the defects, suggesting involvement of alternative mechanisms. Collectively, these findings demonstrate that TBBPA disrupts proteins critical for cell migration, fate specification, and germ layer formation at environmentally relevant concentrations, fundamentally altering embryonic physiology prior to organogenesis and inducing systemic changes in tissue development.
{"title":"Low-level tetrabromobisphenol A (TBBPA) exposure disrupts early embryonic architecture: molecular impacts on dorsoventral patterning","authors":"Kanchaka Senarath Pathirajage , Rosemaria Serradimigni , Copeland R. Johnson , Sunil Sharma , Christopher Chouinard , Subham Dasgupta","doi":"10.1016/j.cbpc.2025.110348","DOIUrl":"10.1016/j.cbpc.2025.110348","url":null,"abstract":"<div><div>Tetrabromobisphenol A (TBBPA), a widely used flame retardant in textiles and electronics, poses toxicological risks through both environmental and indoor exposures. Biomonitoring studies have detected significant TBBPA levels in prenatal environments, including cord blood, raising concerns about developmental impacts. Using zebrafish as a model, this study addresses critical gaps in understanding how developmental TBBPA exposures perturb regulatory pathways that govern dorsoventral patterning. Embryos were exposed at 0.75- or 6-h post-fertilization (hpf) and phenotyped at 24 hpf, with tissue uptake quantified by LC-MS. At 24 hpf, embryos exhibited concentration-dependent ventralization characterized by loss of dorsal structures. Whole-mount immunohistochemistry revealed concentration-dependent alterations in dorsoventral, cell adhesion, and germ layer markers, indicating disruptions in cell migration and germ layer integrity. At later stages, even nontoxic exposures led to craniofacial and hematopoietic defects, linking early molecular perturbations to downstream developmental abnormalities. Although the phenotypes strongly resembled BMP pathway overactivation, co-exposure with the BMP inhibitor dorsomorphin failed to rescue the defects, suggesting involvement of alternative mechanisms. Collectively, these findings demonstrate that TBBPA disrupts proteins critical for cell migration, fate specification, and germ layer formation at environmentally relevant concentrations, fundamentally altering embryonic physiology prior to organogenesis and inducing systemic changes in tissue development.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"299 ","pages":"Article 110348"},"PeriodicalIF":4.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022968","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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