Pub 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":"2025-11-20","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 : 2025-11-19DOI: 10.1016/j.cbpc.2025.110396
Chung-Yu Lin , Wangta Liu , Pei-Hsuan Chen , Chia C. Wang , Che-Hsin Lee
Phenol is a common aquatic contaminant originating from industrial discharge, plastics, and personal care products, and is frequently detected due to its high solubility and environmental persistence. Although its acute toxicity is well documented, the effects of phenol at environmentally relevant concentrations on cellular mechanisms linked to tumor progression remain underexplored. In this study, we investigated the impact of phenol exposure (0–125 μM) on cancer-related cellular behaviors using B16F10 melanoma and LL2 lung carcinoma cells, as well as zebrafish xenograft models, which serve as an integrated aquatic toxicology platform. Phenol exposure activated extracellular signal-regulated kinase (ERK) and p38 pathways, upregulated hypoxia-inducible factor 1α (HIF-1α), increased vascular endothelial growth factor (VEGF) expression, and induced epithelial–mesenchymal transition (EMT). These molecular events collectively enhanced tumor cell migration and angiogenesis both in vitro and in vivo. Our findings provide mechanistic evidence that environmentally relevant phenol exposure can modulate conserved stress and signaling pathways associated with tumor-related phenotypes. This work underscores the importance of combining molecular biomarkers with aquatic vertebrate models to assess the ecological and toxicological risks of persistent organic pollutants such as phenol.
{"title":"Phenol exposure promotes tumor-related signaling and blood vessel formation through the extracellular signal-regulated kinase/p38/hypoxia-inducible factor-1α pathway in cellular and zebrafish models","authors":"Chung-Yu Lin , Wangta Liu , Pei-Hsuan Chen , Chia C. Wang , Che-Hsin Lee","doi":"10.1016/j.cbpc.2025.110396","DOIUrl":"10.1016/j.cbpc.2025.110396","url":null,"abstract":"<div><div>Phenol is a common aquatic contaminant originating from industrial discharge, plastics, and personal care products, and is frequently detected due to its high solubility and environmental persistence. Although its acute toxicity is well documented, the effects of phenol at environmentally relevant concentrations on cellular mechanisms linked to tumor progression remain underexplored. In this study, we investigated the impact of phenol exposure (0–125 μM) on cancer-related cellular behaviors using B16F10 melanoma and LL2 lung carcinoma cells, as well as zebrafish xenograft models, which serve as an integrated aquatic toxicology platform. Phenol exposure activated extracellular signal-regulated kinase (ERK) and p38 pathways, upregulated hypoxia-inducible factor 1α (HIF-1α), increased vascular endothelial growth factor (VEGF) expression, and induced epithelial–mesenchymal transition (EMT). These molecular events collectively enhanced tumor cell migration and angiogenesis both <em>in vitro</em> and <em>in vivo</em>. Our findings provide mechanistic evidence that environmentally relevant phenol exposure can modulate conserved stress and signaling pathways associated with tumor-related phenotypes. This work underscores the importance of combining molecular biomarkers with aquatic vertebrate models to assess the ecological and toxicological risks of persistent organic pollutants such as phenol.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"300 ","pages":"Article 110396"},"PeriodicalIF":4.3,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145562999","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 : 2025-11-19DOI: 10.1016/j.cbpc.2025.110397
Jiejie Li , Yingjie Chen , Yuequn Chen , Han Xie , Ganglong Wu , Yiming Zhang , Kusheng Wu
The widespread use of plastic products has led to the global accumulation of microplastics (MPs) and nanoplastics (NPs) in aquatic and terrestrial environments, posing significant risks to ecosystems and human health. This study investigated the neurodevelopmental toxicity of polystyrene MPs (PS-MPs, 5 μm) and NPs (PS-NPs, 60 nm) in zebrafish (Danio rerio) and explored the underlying mechanisms. Zebrafish embryos were exposed to 0.05–50 mg/L PS-MPs/PS-NPs from 2 hour post-fertilization (hpf) to 7 days post-fertilization (dpf). Morphological, behavioral, and molecular endpoints were analyzed. Exposure to polystyrene MPs and NPs (PS-MNPs) induced dose-dependent developmental malformations, including spinal curvature, pericardial edema, and abnormal body pigmentation, accompanied by increased heart rate and body length. Behavioral assays revealed reduced spontaneous tail-coiling in embryos and hyperactive swimming in larvae, particularly under light stimulation. Mechanistic studies showed PS-MNPs disrupted neurotransmitter homeostasis (reduced dopamine, acetylcholine, GABA, and serotonin levels) and altered neurodevelopment-related gene expression (e.g., mbpa, ache, gfap). Oxidative stress was evident via elevated reactive oxygen species (ROS) and upregulated antioxidant genes (sod1, cat) in PS-NP-exposed larvae. These findings demonstrate that PS-MNPs induce neurodevelopmental toxicity in zebrafish through oxidative stress and neurotransmitter system dysfunction, highlighting the potential risks of plastic pollution to aquatic organisms and human health via trophic transfer.
{"title":"Polystyrene microplastics and nanoplastics induce neurotoxicity in zebrafish via oxidative stress and neurotransmitter disruption","authors":"Jiejie Li , Yingjie Chen , Yuequn Chen , Han Xie , Ganglong Wu , Yiming Zhang , Kusheng Wu","doi":"10.1016/j.cbpc.2025.110397","DOIUrl":"10.1016/j.cbpc.2025.110397","url":null,"abstract":"<div><div>The widespread use of plastic products has led to the global accumulation of microplastics (MPs) and nanoplastics (NPs) in aquatic and terrestrial environments, posing significant risks to ecosystems and human health. This study investigated the neurodevelopmental toxicity of polystyrene MPs (PS-MPs, 5 μm) and NPs (PS-NPs, 60 nm) in zebrafish (<em>Danio rerio</em>) and explored the underlying mechanisms. Zebrafish embryos were exposed to 0.05–50 mg/L PS-MPs/PS-NPs from 2 hour post-fertilization (hpf) to 7 days post-fertilization (dpf). Morphological, behavioral, and molecular endpoints were analyzed. Exposure to polystyrene MPs and NPs (PS-MNPs) induced dose-dependent developmental malformations, including spinal curvature, pericardial edema, and abnormal body pigmentation, accompanied by increased heart rate and body length. Behavioral assays revealed reduced spontaneous tail-coiling in embryos and hyperactive swimming in larvae, particularly under light stimulation. Mechanistic studies showed PS-MNPs disrupted neurotransmitter homeostasis (reduced dopamine, acetylcholine, GABA, and serotonin levels) and altered neurodevelopment-related gene expression (e.g., <em>mbpa, ache, gfap</em>). Oxidative stress was evident via elevated reactive oxygen species (ROS) and upregulated antioxidant genes (<em>sod1, cat</em>) in PS-NP-exposed larvae. These findings demonstrate that PS-MNPs induce neurodevelopmental toxicity in zebrafish through oxidative stress and neurotransmitter system dysfunction, highlighting the potential risks of plastic pollution to aquatic organisms and human health via trophic transfer.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"300 ","pages":"Article 110397"},"PeriodicalIF":4.3,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145562994","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 : 2025-11-19DOI: 10.1016/j.cbpc.2025.110393
Hojun Lee , Jisoo Song , Garam An , Seung-Min Bae , Gwonhwa Song , Whasun Lim , Sunwoo Park
Flusilazole is a triazole-based fungicide that persists in various environments because of its high stability and solubility, raising concerns about its developmental and ecological impacts. Although numerous studies have reported flusilazole-induced toxicity, the specific effects and mechanisms of flusilazole-induced hepatotoxicity during development remain unclear. In this study, we examined the in vivo and in vitro toxicities in Danio rerio (zebrafish) and zebrafish-derived liver (ZFL) cells. Morphological changes in the liver and alterations in liver regeneration were evaluated using fabp10a:dsRed and fabp10a:CFP-NTR transgenic models. Flusilazole exposure was shown to deteriorate hepatic structure and regenerative capacity, with potential long-term consequences for aquatic organisms. Moreover, in ZFL cells, flusilazole treatment induced oxidative stress, mitochondrial malfunction, and disruption of calcium and iron homeostasis, leading to the induction of apoptosis and ferroptosis. Transcriptomic analysis supported these findings. Additionally, disturbances in ERK and Akt signaling indicated interference with pathways central to cell survival, growth, and tissue repair. Together, these findings establish that flusilazole exerts developmental hepatotoxic effects and highlight its potential hazards to ecosystems.
{"title":"Developmental hepatotoxicity induced by flusilazole in zebrafish: Mechanistic insights into mitochondrial dysfunction, oxidative stress, ferroptosis, and regenerative impairment","authors":"Hojun Lee , Jisoo Song , Garam An , Seung-Min Bae , Gwonhwa Song , Whasun Lim , Sunwoo Park","doi":"10.1016/j.cbpc.2025.110393","DOIUrl":"10.1016/j.cbpc.2025.110393","url":null,"abstract":"<div><div>Flusilazole is a triazole-based fungicide that persists in various environments because of its high stability and solubility, raising concerns about its developmental and ecological impacts. Although numerous studies have reported flusilazole-induced toxicity, the specific effects and mechanisms of flusilazole-induced hepatotoxicity during development remain unclear. In this study, we examined the <em>in vivo</em> and <em>in vitro</em> toxicities in <em>Danio rerio</em> (zebrafish) and zebrafish-derived liver (ZFL) cells. Morphological changes in the liver and alterations in liver regeneration were evaluated using <em>fabp10a:dsRed</em> and <em>fabp10a:CFP-NTR</em> transgenic models. Flusilazole exposure was shown to deteriorate hepatic structure and regenerative capacity, with potential long-term consequences for aquatic organisms. Moreover, in ZFL cells, flusilazole treatment induced oxidative stress, mitochondrial malfunction, and disruption of calcium and iron homeostasis, leading to the induction of apoptosis and ferroptosis. Transcriptomic analysis supported these findings. Additionally, disturbances in ERK and Akt signaling indicated interference with pathways central to cell survival, growth, and tissue repair. Together, these findings establish that flusilazole exerts developmental hepatotoxic effects and highlight its potential hazards to ecosystems.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"300 ","pages":"Article 110393"},"PeriodicalIF":4.3,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145563091","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 : 2025-11-19DOI: 10.1016/j.cbpc.2025.110399
Yahui Wu , Qing Huang
Astaxanthin (AST) as a natural carotenoid exhibits potent antioxidant and anti-inflammatory capacities. This work investigated AST’s protective effects against microcystin-LR (MC-LR) toxicity to zebrafish embryos. When the zebrafish embryos were exposed to a sublethal, environmentally relevant concentration of MC-LR (10 μg/L, approximately half of the LC50 value), AST (100 μg/L) could significantly reduce MC-LR-induced mortality by 39.8% and deformity rates by 60.0%. Furthermore, AST decreased ROS and MDA levels by 11.0% and 14.5%, respectively, and enhanced the activities of superoxide dismutase (SOD, 4.4-fold), catalase (CAT, 1.2-fold), and glutathione reductase (GR, 1.6-fold). It also ameliorated MC-LR-induced inflammatory responses, as evidenced by a 49.1% reduction in neutral red staining, a 42.0% to 42.9% improvement in host resistance, and a significant down-regulation of major cytokines (IL-1β, IL-6, IL-8, TNF-α) by 0.4 to 0.6-fold. Analysis of the transcriptome revealed that AST can inhibit the C-type lectin receptor signaling pathway and others to counteract the inflammatory and oxidative stress induced by MC-LR. Our findings confirm that AST neutralizes the toxicity of MC-LR through the mechanisms of antagonizing oxidative stress, exhibiting anti-inflammatory and immunomodulatory effects, which may pave the way for AST being used in aquaculture and environmental health.
{"title":"Astaxanthin mitigates the inflammatory toxicity of microcystin-LR on zebrafish embryos","authors":"Yahui Wu , Qing Huang","doi":"10.1016/j.cbpc.2025.110399","DOIUrl":"10.1016/j.cbpc.2025.110399","url":null,"abstract":"<div><div>Astaxanthin (AST) as a natural carotenoid exhibits potent antioxidant and anti-inflammatory capacities. This work investigated AST’s protective effects against microcystin-LR (MC-LR) toxicity to zebrafish embryos. When the zebrafish embryos were exposed to a sublethal, environmentally relevant concentration of MC-LR (10 μg/L, approximately half of the LC<sub>50</sub> value), AST (100 μg/L) could significantly reduce MC-LR-induced mortality by 39.8% and deformity rates by 60.0%. Furthermore, AST decreased ROS and MDA levels by 11.0% and 14.5%, respectively, and enhanced the activities of superoxide dismutase (SOD, 4.4-fold), catalase (CAT, 1.2-fold), and glutathione reductase (GR, 1.6-fold). It also ameliorated MC-LR-induced inflammatory responses, as evidenced by a 49.1% reduction in neutral red staining, a 42.0% to 42.9% improvement in host resistance, and a significant down-regulation of major cytokines (IL-1β, IL-6, IL-8, TNF-α) by 0.4 to 0.6-fold. Analysis of the transcriptome revealed that AST can inhibit the C-type lectin receptor signaling pathway and others to counteract the inflammatory and oxidative stress induced by MC-LR. Our findings confirm that AST neutralizes the toxicity of MC-LR through the mechanisms of antagonizing oxidative stress, exhibiting anti-inflammatory and immunomodulatory effects, which may pave the way for AST being used in aquaculture and environmental health.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"300 ","pages":"Article 110399"},"PeriodicalIF":4.3,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145573364","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}
Di-ethylhexyl phthalate (DEHP) is an endocrine disruptor with established neurotoxic as well as potential neurodegenerative effects. The myelin sheath plays a crucial role in maintaining the health of the nervous system, whereas demyelination contributes to the onset of brain diseases. This study investigated the effect of DEHP on the neurological development with special reference to endoplasmic reticulum (ER) stress, inflammation, and concurrently with demyelination and cellular apoptotic development in zebrafish larvae. Results indicated that DEHP exposure can lead to demyelination through ER stress and inflammation, as evident from the decreased expression of myelin basic protein (Mbp) in both the brain and spinal cord of zebrafish larvae analyzed through immunofluorescent assay. The mRNA expression of axon marker nfl significantly increased, while tuba1a was decreased with DEHP exposure. Western blotting analysis revealed that ER stress markers such as phosphorylated inositol-requiring enzyme 1 alpha (p-Ire1α), activating transcription factor 4 (Atf4), binding immunoglobulin protein (Bip), phosphorylated e-IF2 alpha (p-eIF2α), CCAAT/enhancer-binding protein homologous protein (Chop), and inflammatory markers (nuclear factor kappa B subunit p65; Nf-κb p65), ionized calcium-binding adaptor molecule 1 (Iba1), and glial fibrillary acid protein (Gfap), were significantly upregulated on exposure to DEHP. Scototaxis, a behavioral assay, showed an altered anxiety-like behaviour in DEHP-treated larvae. Oxidative stress markers, such as superoxide dismutase (SOD), catalase, and monoamine oxidase (MAO) were also elevated. Apoptotic cells were observed in DEHP-treated zebrafish larvae in acridine orange staining. Overall, the DEHP exposure to zebrafish larvae caused myelin sheath degeneration and axonal dysfunction due to the generation of ER stress and inflammation.
{"title":"Concurrent endoplasmic reticulum stress and demyelination in DEHP-exposed zebrafish larvae at the early developmental stages","authors":"Garima Jindal , Anuradha Mangla , Mehjbeen Javed , Mohd. Anas Saifi , Iqra Mazahir , Padmshree Mudgal , Shiekh Raisuddin","doi":"10.1016/j.cbpc.2025.110394","DOIUrl":"10.1016/j.cbpc.2025.110394","url":null,"abstract":"<div><div>Di-ethylhexyl phthalate (DEHP) is an endocrine disruptor with established neurotoxic as well as potential neurodegenerative effects. The myelin sheath plays a crucial role in maintaining the health of the nervous system, whereas demyelination contributes to the onset of brain diseases. This study investigated the effect of DEHP on the neurological development with special reference to endoplasmic reticulum (ER) stress, inflammation, and concurrently with demyelination and cellular apoptotic development in zebrafish larvae. Results indicated that DEHP exposure can lead to demyelination through ER stress and inflammation, as evident from the decreased expression of myelin basic protein (Mbp) in both the brain and spinal cord of zebrafish larvae analyzed through immunofluorescent assay. The mRNA expression of axon marker <em>nfl</em> significantly increased, while <em>tuba1a</em> was decreased with DEHP exposure. Western blotting analysis revealed that ER stress markers such as phosphorylated inositol-requiring enzyme 1 alpha (p-Ire1α), activating transcription factor 4 (Atf4), binding immunoglobulin protein (Bip), phosphorylated e-IF2 alpha (p-eIF2α), CCAAT/enhancer-binding protein homologous protein (Chop), and inflammatory markers (nuclear factor kappa B subunit p65; Nf-κb p65), ionized calcium-binding adaptor molecule 1 (Iba1), and glial fibrillary acid protein (Gfap), were significantly upregulated on exposure to DEHP. Scototaxis, a behavioral assay, showed an altered anxiety-like behaviour in DEHP-treated larvae. Oxidative stress markers, such as superoxide dismutase (SOD), catalase, and monoamine oxidase (MAO) were also elevated. Apoptotic cells were observed in DEHP-treated zebrafish larvae in acridine orange staining. Overall, the DEHP exposure to zebrafish larvae caused myelin sheath degeneration and axonal dysfunction due to the generation of ER stress and inflammation.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"301 ","pages":"Article 110394"},"PeriodicalIF":4.3,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145563064","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 : 2025-11-14DOI: 10.1016/j.cbpc.2025.110389
Luana Granada , Inês F.C. Morão , Marco F.L. Lemos , Peter Bossier , Sara C. Novais
The rotifer Brachionus sp. is of great importance for aquaculture, as the reproduction cycle under rearing conditions of many economically important species larvae depends on the use of rotifers as first live feed. Establishing a protocol that results in an improved tolerance of rotifers to environmental stressors will allow for a more stable rotifer production. The exposure to non-lethal heat shocks (NLHS) already proved to enhance the tolerance, not only to heat stress, but also to other stressors in several aquatic species, by activating the heat shock response and epigenetic mechanisms. This study aimed to determine the potential of a single NLHS to induce tolerance to different abiotic stressors in two strains of B. koreanus (MRS10 and IBA3) and to evaluate possible molecular mechanisms involved in the achievement of increased tolerance to hydrogen peroxide induced by NLHS. Cross-tolerance was achieved for both strains, namely to high salinity, cadmium chloride, and hydrogen peroxide. Scale-up tests resulted in increased tolerance to hydrogen peroxide only for MRS10. During the exposure to this substance, heat-shocked MRS10 rotifers showed an up-regulation of genes related to oxidative stress response and histone modifications, increased production of HSP70, and higher levels of total acetylation of histone H3. A single NLHS proved to induce epigenetic effects when rotifers were exposed to other stressor later in life. However, further studies should elucidate if the NLHS conditions used in this study can yield a persistent outcome, allowing the establishment of tolerant rotifer strain lines and, consequently, a more stable production.
{"title":"Non-lethal heat shock induces cross-tolerance to different stressors in two strains of Brachionus koreanus (Rotifera: Monogononta): Mechanisms of increased tolerance to hydrogen peroxide","authors":"Luana Granada , Inês F.C. Morão , Marco F.L. Lemos , Peter Bossier , Sara C. Novais","doi":"10.1016/j.cbpc.2025.110389","DOIUrl":"10.1016/j.cbpc.2025.110389","url":null,"abstract":"<div><div>The rotifer <em>Brachionus</em> sp. is of great importance for aquaculture, as the reproduction cycle under rearing conditions of many economically important species larvae depends on the use of rotifers as first live feed. Establishing a protocol that results in an improved tolerance of rotifers to environmental stressors will allow for a more stable rotifer production. The exposure to non-lethal heat shocks (NLHS) already proved to enhance the tolerance, not only to heat stress, but also to other stressors in several aquatic species, by activating the heat shock response and epigenetic mechanisms. This study aimed to determine the potential of a single NLHS to induce tolerance to different abiotic stressors in two strains of <em>B. koreanus</em> (MRS10 and IBA3) and to evaluate possible molecular mechanisms involved in the achievement of increased tolerance to hydrogen peroxide induced by NLHS. Cross-tolerance was achieved for both strains, namely to high salinity, cadmium chloride, and hydrogen peroxide. Scale-up tests resulted in increased tolerance to hydrogen peroxide only for MRS10. During the exposure to this substance, heat-shocked MRS10 rotifers showed an up-regulation of genes related to oxidative stress response and histone modifications, increased production of HSP70, and higher levels of total acetylation of histone H3. A single NLHS proved to induce epigenetic effects when rotifers were exposed to other stressor later in life. However, further studies should elucidate if the NLHS conditions used in this study can yield a persistent outcome, allowing the establishment of tolerant rotifer strain lines and, consequently, a more stable production.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"300 ","pages":"Article 110389"},"PeriodicalIF":4.3,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534408","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 : 2025-11-13DOI: 10.1016/j.cbpc.2025.110390
Anqi Liu , Kun Chen , Xuchun Qiu , Yuki Takai , Yohei Shimasaki , Yuji Oshima
Amitriptyline (AMI), a commonly used tricyclic antidepressant, has been identified as a significant pharmaceutical contaminant in aquatic environments. Although parental exposure of zebrafish to AMI has been found to induce changes in the development, behavior, and gene expression of their F1 offspring, it is unclear whether such adverse effects will be further extended to subsequent generations. In the current study, we explored the effects of ancestral exposure to AMI at environmentally relevant concentrations (0 and 0.8 μg/L) on the early life stages of zebrafish F2 offspring. The results showed that ancestral exposure to AMI had no significant effect on the survival and development of the zebrafish F2 offspring. However, significant hyperactivity was observed in the F2 larvae in the ancestral AMI exposure group during the dark periods of a light-dark locomotion assay. Transcription analysis revealed that ancestral exposure to AMI significantly disrupted pathways associated with xenobiotic biodegradation and metabolism, as well as the metabolism of cofactors and vitamins. Furthermore, ancestral exposure to AMI significantly decreased the level of cytochrome P450 and the activity of glutathione S-transferase within the F2 larvae, which are critical enzymes involved in xenobiotic metabolism. These findings provide valuable insights into the multigenerational effects of AMI exposure in zebrafish, emphasizing the importance of assessing the risks posed by such pollutants to fish populations.
{"title":"Ancestral exposure to amitriptyline disrupts the behavior and gene expression in zebrafish F2 offspring","authors":"Anqi Liu , Kun Chen , Xuchun Qiu , Yuki Takai , Yohei Shimasaki , Yuji Oshima","doi":"10.1016/j.cbpc.2025.110390","DOIUrl":"10.1016/j.cbpc.2025.110390","url":null,"abstract":"<div><div>Amitriptyline (AMI), a commonly used tricyclic antidepressant, has been identified as a significant pharmaceutical contaminant in aquatic environments. Although parental exposure of zebrafish to AMI has been found to induce changes in the development, behavior, and gene expression of their F1 offspring, it is unclear whether such adverse effects will be further extended to subsequent generations. In the current study, we explored the effects of ancestral exposure to AMI at environmentally relevant concentrations (0 and 0.8 μg/L) on the early life stages of zebrafish F2 offspring. The results showed that ancestral exposure to AMI had no significant effect on the survival and development of the zebrafish F2 offspring. However, significant hyperactivity was observed in the F2 larvae in the ancestral AMI exposure group during the dark periods of a light-dark locomotion assay. Transcription analysis revealed that ancestral exposure to AMI significantly disrupted pathways associated with xenobiotic biodegradation and metabolism, as well as the metabolism of cofactors and vitamins. Furthermore, ancestral exposure to AMI significantly decreased the level of cytochrome P450 and the activity of glutathione S-transferase within the F2 larvae, which are critical enzymes involved in xenobiotic metabolism. These findings provide valuable insights into the multigenerational effects of AMI exposure in zebrafish, emphasizing the importance of assessing the risks posed by such pollutants to fish populations.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"300 ","pages":"Article 110390"},"PeriodicalIF":4.3,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145530475","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 : 2025-11-13DOI: 10.1016/j.cbpc.2025.110392
Davide Asnicar , Benjamin de Jourdan
Azamethiphos and hydrogen peroxide are active ingredients (AI) of formulations used as water-bath pesticides in Atlantic salmon aquaculture to remove ectoparasitic copepods. Despite their long-term use, unknowns and concerns are still present, particularly regarding the toxicity towards non-target commercially and ecologically important species in Atlantic Canada, and potential differences in toxicity between the AI and the formulated product.
Here, we tested the acute effects of azamethiphos and hydrogen peroxide on five marine species. Hazard data (half maximal effective and lethal concentrations, respectively EC50 and LC50) were determined for 10 endpoints, assessed at various timepoints, during the exposure of Stage I larval American lobster Homarus americanus, green sea urchin Strongylocentrotus droebachiensis gametes, haemocytes and adults of blue mussel Mytilus edulis, common periwinkle snail Littorina littorea, and copepod Acartia tonsa.
To investigate whether formulations had the same effect as the AI, for azamethiphos, both the AI and the formulation (Salmosan® Vet) were tested. For hydrogen peroxide, potential differences in the toxicity of three formulations (purchased solutions 50 %, 35 %, and 3 %) were compared.
Results suggest no differences between the azamethiphos and Salmosan® Vet, with similar L/EC50 values. Little differences were found among the three hydrogen peroxide formulations. For azamethiphos, the most sensitive species was the American lobster, followed by sea urchin, whereas for hydrogen peroxide, sea urchin was the most sensitive, followed by A. tonsa. L. littorea was the least sensitive species tested. Overall, results showed that all the endpoints were greater than the Environmental Quality Standard previously determined for the two compounds.
{"title":"Anti-sea lice products azamethiphos and hydrogen peroxide effects on five coastal marine organisms","authors":"Davide Asnicar , Benjamin de Jourdan","doi":"10.1016/j.cbpc.2025.110392","DOIUrl":"10.1016/j.cbpc.2025.110392","url":null,"abstract":"<div><div>Azamethiphos and hydrogen peroxide are active ingredients (AI) of formulations used as water-bath pesticides in Atlantic salmon aquaculture to remove ectoparasitic copepods. Despite their long-term use, unknowns and concerns are still present, particularly regarding the toxicity towards non-target commercially and ecologically important species in Atlantic Canada, and potential differences in toxicity between the AI and the formulated product.</div><div>Here, we tested the acute effects of azamethiphos and hydrogen peroxide on five marine species. Hazard data (half maximal effective and lethal concentrations, respectively EC50 and LC50) were determined for 10 endpoints, assessed at various timepoints, during the exposure of Stage I larval American lobster <em>Homarus americanus</em>, green sea urchin <em>Strongylocentrotus droebachiensis</em> gametes, haemocytes and adults of blue mussel <em>Mytilus edulis</em>, common periwinkle snail <em>Littorina littorea</em>, and copepod <em>Acartia tonsa</em>.</div><div>To investigate whether formulations had the same effect as the AI, for azamethiphos, both the AI and the formulation (Salmosan® Vet) were tested. For hydrogen peroxide, potential differences in the toxicity of three formulations (purchased solutions 50 %, 35 %, and 3 %) were compared.</div><div>Results suggest no differences between the azamethiphos and Salmosan® Vet, with similar L/EC50 values. Little differences were found among the three hydrogen peroxide formulations. For azamethiphos, the most sensitive species was the American lobster, followed by sea urchin, whereas for hydrogen peroxide, sea urchin was the most sensitive, followed by <em>A. tonsa</em>. <em>L. littorea</em> was the least sensitive species tested. Overall, results showed that all the endpoints were greater than the Environmental Quality Standard previously determined for the two compounds.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"300 ","pages":"Article 110392"},"PeriodicalIF":4.3,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145530464","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}
Cyanotoxins are one of the major threats to aquatic ecosystems due to their diverse toxic effects on aquatic organisms. Cylindrospermopsin is a globally reported freshwater cyanotoxin that exhibits hepatotoxic, cytotoxic, immunotoxic, and neurotoxic effects in teleosts; however, its harmful effects on reproductive health remain less explored. This study investigates the impacts of cylindrospermopsin on the reproductive endocrine and paracrine system, emphasising the HPGL axis of female zebrafish. Following 14 days of in-vivo cylindrospermopsin exposure, decreased gonadosomatic and hepatosomatic indices were observed. The number of fully grown (vitellogenic and post-vitellogenic) oocytes was decreased in treated groups, signifying oocyte growth impairments. Disruption of serum gonadotropin levels (FSH and LH) and steroid (17β-estradiol/testosterone) ratio was also observed, indicating the endocrine-disrupting effects of cylindrospermopsin. Following in-vitro cylindrospermopsin exposure for 8 h, increased GVBD was observed, representing early oocyte maturation. Besides endocrine regulation, stress-induced immune-activation of paracrine factors also regulates oocyte maturation. Subsequently, elevated lipid peroxidation and antioxidant activity were observed in the ovary of exposed groups, which disrupts the expression of different steroidogenesis and antioxidant marker genes. This is followed by upregulated expression of paracrine factors: nf-κb, tnf-α and il-1β genes in the ovary, which further activates the apoptotic cascade in the CYN-treated oocytes by upregulating p53, bax, casp3 and suppressing bcl2 gene expression. This revealed that cylindrospermopsin is an effective endocrine disruptor that induces reproductive toxicity by promoting oxidative stress and inducing early oocyte maturation by immune-activation of the NF-κB/TNF-α pathway, emphasising the importance of deciphering its ecotoxicological risk.
{"title":"Chronic cylindrospermopsin exposure impairs oocyte growth and maturation by stress-induced endocrine disruption and immune activation of NF-κB/TNF-α pathway in female zebrafish","authors":"Chayan Biswas, Madhuchhanda Adhikari, Kousik Pramanick","doi":"10.1016/j.cbpc.2025.110387","DOIUrl":"10.1016/j.cbpc.2025.110387","url":null,"abstract":"<div><div>Cyanotoxins are one of the major threats to aquatic ecosystems due to their diverse toxic effects on aquatic organisms. Cylindrospermopsin is a globally reported freshwater cyanotoxin that exhibits hepatotoxic, cytotoxic, immunotoxic, and neurotoxic effects in teleosts; however, its harmful effects on reproductive health remain less explored. This study investigates the impacts of cylindrospermopsin on the reproductive endocrine and paracrine system, emphasising the HPGL axis of female zebrafish. Following 14 days of <em>in-vivo</em> cylindrospermopsin exposure, decreased gonadosomatic and hepatosomatic indices were observed. The number of fully grown (vitellogenic and post-vitellogenic) oocytes was decreased in treated groups, signifying oocyte growth impairments. Disruption of serum gonadotropin levels (FSH and LH) and steroid (17β-estradiol/testosterone) ratio was also observed, indicating the endocrine-disrupting effects of cylindrospermopsin. Following <em>in-vitro</em> cylindrospermopsin exposure for 8 h, increased GVBD was observed, representing early oocyte maturation. Besides endocrine regulation, stress-induced immune-activation of paracrine factors also regulates oocyte maturation. Subsequently, elevated lipid peroxidation and antioxidant activity were observed in the ovary of exposed groups, which disrupts the expression of different steroidogenesis and antioxidant marker genes. This is followed by upregulated expression of paracrine factors: <em>nf-κb</em>, <em>tnf-α</em> and <em>il-1β</em> genes in the ovary, which further activates the apoptotic cascade in the CYN-treated oocytes by upregulating <em>p53, bax, casp3</em> and suppressing <em>bcl2</em> gene expression. This revealed that cylindrospermopsin is an effective endocrine disruptor that induces reproductive toxicity by promoting oxidative stress and inducing early oocyte maturation by immune-activation of the NF-κB/TNF-α pathway, emphasising the importance of deciphering its ecotoxicological risk.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"300 ","pages":"Article 110387"},"PeriodicalIF":4.3,"publicationDate":"2025-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145480561","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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