Pub Date : 2026-02-01Epub 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":"2026-02-01","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 : 2026-02-01Epub Date: 2025-11-01DOI: 10.1016/j.cbpc.2025.110384
Jaehee Kim , Seong Duk Do , Jae-Sung Rhee
Despite being persistent pollutants of global concern and frequently detected in aquatic environments, the detrimental effects of short-chain chlorinated paraffins (SCCPs) on aquatic crustaceans remain limited. Here, we analyzed the acute and chronic effects of SCCPs on the freshwater flea Moina macrocopa. The no observed effect concentration (NOEC) value of SCCPs for 48 h was determined to be 0.24 μg L−1, while the 10 % (LC10) and 50 % (LC50) lethality values were measured as 3.7 and 36 μg L−1, respectively. In the acute exposure experiment, exposure to the LC10 value of SCCPs reduced feeding performance, acetylcholinesterase activity, and thoracic limb movement. In response to the LC10 value, reactive oxygen species levels increased, accompanied by elevated concentrations of malondialdehyde and glutathione. Enzymatic activities of glutathione S-transferase, catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase were significantly elevated at the LC10 value, indicating active involvement of the antioxidant defense system in mitigating oxidative stress. Long-term exposure to the 1/10 NOEC and NOEC values across three generations showed multigenerational detrimental impacts of SCCPs, including reductions in survival, growth, and reproduction in the second and/or third generations. Taken together, our results suggest that even sublethal concentrations of SCCPs can acutely induce cholinergic impairment and oxidative stress, while chronically impairing population maintenance in M. macrocopa.
{"title":"Effects of short-chain chlorinated paraffins on feeding, oxidative status, and multigenerational parameters in the water flea Moina macrocopa","authors":"Jaehee Kim , Seong Duk Do , Jae-Sung Rhee","doi":"10.1016/j.cbpc.2025.110384","DOIUrl":"10.1016/j.cbpc.2025.110384","url":null,"abstract":"<div><div>Despite being persistent pollutants of global concern and frequently detected in aquatic environments, the detrimental effects of short-chain chlorinated paraffins (SCCPs) on aquatic crustaceans remain limited. Here, we analyzed the acute and chronic effects of SCCPs on the freshwater flea <em>Moina macrocopa</em>. The no observed effect concentration (NOEC) value of SCCPs for 48 h was determined to be 0.24 μg L<sup>−1</sup>, while the 10 % (LC10) and 50 % (LC50) lethality values were measured as 3.7 and 36 μg L<sup>−1</sup>, respectively. In the acute exposure experiment, exposure to the LC10 value of SCCPs reduced feeding performance, acetylcholinesterase activity, and thoracic limb movement. In response to the LC10 value, reactive oxygen species levels increased, accompanied by elevated concentrations of malondialdehyde and glutathione. Enzymatic activities of glutathione <em>S</em>-transferase, catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase were significantly elevated at the LC10 value, indicating active involvement of the antioxidant defense system in mitigating oxidative stress. Long-term exposure to the 1/10 NOEC and NOEC values across three generations showed multigenerational detrimental impacts of SCCPs, including reductions in survival, growth, and reproduction in the second and/or third generations. Taken together, our results suggest that even sublethal concentrations of SCCPs can acutely induce cholinergic impairment and oxidative stress, while chronically impairing population maintenance in <em>M. macrocopa</em>.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"300 ","pages":"Article 110384"},"PeriodicalIF":4.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145437270","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 : 2026-02-01Epub 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":"2026-02-01","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 : 2026-02-01Epub Date: 2025-10-31DOI: 10.1016/j.cbpc.2025.110380
Jinhao Bian , Hanshuang Zhao , Wenping Xu , Zhong Li , Yang Zhang
The widespread use of prothioconazole (PTCZ), a globally applied triazole fungicide, raises concerns regarding ecological risks from environmental residues and highlights the critical gap in pesticide safety assessment concerning enantiomeric differences in toxicity. This study investigated the stereoselective toxicity and molecular mechanisms of PTCZ enantiomers in an aquatic model using a zebrafish embryo exposure system. The toxic effects were systematically analyzed through multidimensional endpoint assessments, which examined developmental malformations, liver histopathology, lipid metabolism indicators, and lipid peroxidation. The underlying molecular mechanisms were explored through GPX4 immunofluorescence, as well as qPCR and Western blot analyses of ferroptosis-related genes. A ferroptosis inhibitor rescue experiment utilizing Ferrostatin-1 was conducted to investigate the role of ferroptosis in the observed toxicity. Our findings demonstrate that the S-(+)-PTCZ enantiomer induced significantly more severe developmental toxicity and liver injury compared to its counterpart. Mechanistically, S-(+)-PTCZ triggered hepatic damage by activating the lipid peroxidation-ferroptosis axis, as evidenced by inhibition of GPX4 protein expression and an upregulation of the pro-ferroptotic gene acsl4. Crucially, Ferrostatin-1 significantly reversed these effects, reducing lipid peroxidation. Our results confirm that traditional risk assessments based on the racemate (Rac-PTCZ) would substantially underestimate the actual environmental risk posed by the highly non-target bioactive S-(+)-enantiomer. This work provides a critical theoretical basis for the precise regulation and low-toxicity design of chiral pesticides.
{"title":"Prothioconazole induced stereoselective developmental toxicity and liver injury in zebrafish embryos via ferroptosis","authors":"Jinhao Bian , Hanshuang Zhao , Wenping Xu , Zhong Li , Yang Zhang","doi":"10.1016/j.cbpc.2025.110380","DOIUrl":"10.1016/j.cbpc.2025.110380","url":null,"abstract":"<div><div>The widespread use of prothioconazole (PTCZ), a globally applied triazole fungicide, raises concerns regarding ecological risks from environmental residues and highlights the critical gap in pesticide safety assessment concerning enantiomeric differences in toxicity. This study investigated the stereoselective toxicity and molecular mechanisms of PTCZ enantiomers in an aquatic model using a zebrafish embryo exposure system. The toxic effects were systematically analyzed through multidimensional endpoint assessments, which examined developmental malformations, liver histopathology, lipid metabolism indicators, and lipid peroxidation. The underlying molecular mechanisms were explored through GPX4 immunofluorescence, as well as qPCR and Western blot analyses of ferroptosis-related genes. A ferroptosis inhibitor rescue experiment utilizing Ferrostatin-1 was conducted to investigate the role of ferroptosis in the observed toxicity. Our findings demonstrate that the S-(+)-PTCZ enantiomer induced significantly more severe developmental toxicity and liver injury compared to its counterpart. Mechanistically, S-(+)-PTCZ triggered hepatic damage by activating the lipid peroxidation-ferroptosis axis, as evidenced by inhibition of GPX4 protein expression and an upregulation of the pro-ferroptotic gene <em>acsl4</em>. Crucially, Ferrostatin-1 significantly reversed these effects, reducing lipid peroxidation. Our results confirm that traditional risk assessments based on the racemate (Rac-PTCZ) would substantially underestimate the actual environmental risk posed by the highly non-target bioactive S-(+)-enantiomer. This work provides a critical theoretical basis for the precise regulation and low-toxicity design of chiral pesticides.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"300 ","pages":"Article 110380"},"PeriodicalIF":4.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145430344","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 : 2026-02-01Epub Date: 2025-10-31DOI: 10.1016/j.cbpc.2025.110381
Deok-Seo Yoon , Jin-Hyoung Kim , Il-Chan Kim , Youji Wang , Zhou Yang , Min-Chul Lee , Jae-Seong Lee
Aquatic environments are dynamic systems where multiple factors influence the intricate interactions between hosts and their gut microbiomes. This review explores how various stressors alter the gut microbiota of fish and aquatic invertebrates, by examining factors that include water characteristics, photoperiod, external pollutants such as heavy metals and microplastics, food availability, and practical aquaculture feed additives, for example, ethoxyquin. Across these diverse factors, common patterns emerge, including disruptions to microbial diversity, compromised gut barrier integrity, and the induction of oxidative stress. Conversely, beneficial additives like probiotics and astaxanthin are shown to mitigate these negative effects by reinforcing gut structure and modulating the microbial community. Collectively, these findings underscore the critical role of the gut microbiota in mediating host responses to environmental changes. Future research should therefore focus on elucidating specific toxicological pathways like the gut-organ axis, investigating the transgenerational effects of pollutants, and developing probiotic-based strategies to enhance the resilience and sustainability of aquaculture.
{"title":"Effects of environmental factors on host-microbiota interactions in the guts of aquatic organisms: A review","authors":"Deok-Seo Yoon , Jin-Hyoung Kim , Il-Chan Kim , Youji Wang , Zhou Yang , Min-Chul Lee , Jae-Seong Lee","doi":"10.1016/j.cbpc.2025.110381","DOIUrl":"10.1016/j.cbpc.2025.110381","url":null,"abstract":"<div><div>Aquatic environments are dynamic systems where multiple factors influence the intricate interactions between hosts and their gut microbiomes. This review explores how various stressors alter the gut microbiota of fish and aquatic invertebrates, by examining factors that include water characteristics, photoperiod, external pollutants such as heavy metals and microplastics, food availability, and practical aquaculture feed additives, for example, ethoxyquin. Across these diverse factors, common patterns emerge, including disruptions to microbial diversity, compromised gut barrier integrity, and the induction of oxidative stress. Conversely, beneficial additives like probiotics and astaxanthin are shown to mitigate these negative effects by reinforcing gut structure and modulating the microbial community. Collectively, these findings underscore the critical role of the gut microbiota in mediating host responses to environmental changes. Future research should therefore focus on elucidating specific toxicological pathways like the gut-organ axis, investigating the transgenerational effects of pollutants, and developing probiotic-based strategies to enhance the resilience and sustainability of aquaculture.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"300 ","pages":"Article 110381"},"PeriodicalIF":4.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145430110","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 : 2026-02-01Epub 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":"2026-02-01","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}
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":"2026-02-01","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}
Pub Date : 2026-02-01Epub 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":"2026-02-01","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}
Pub Date : 2026-02-01Epub Date: 2025-11-04DOI: 10.1016/j.cbpc.2025.110383
Marta Cunha , Alessio Lenzi , Constança Figueiredo , Lucia De Marchi , Carla Leite , Tania Russo , Gianfranca Monni , Valentina Meucci , Amadeu M.V.M. Soares , Gianluca Polese , Eduarda Pereira , Carlo Pretti , Rosa Freitas
Environmental salinity shifts, intensified by climate change, can influence the toxicity of pollutants such as antibiotics in marine organisms. In this study, specimens of the mussel Mytilus galloprovincialis were exposed for 28 days to three salinity levels (20, 30, and 40) in the presence or absence of tetracycline (TC) (1 mg/L). At the end of the exposure period, the effects were evaluated using an integrated metabolomic, biochemical, and histopathological approach. Tetracycline bioaccumulation did not differ significantly across salinities, indicating that biological effects were driven by stressor interactions rather than uptake. Metabolomic profiling showed that salinity and salinity-TC combinations had stronger impacts than TC alone. At salinity 20, mussels exhibited early oxidative stress and metabolic adjustments, along with tissue atrophy and lipofuscin buildup. Mussels at salinity 30 displayed relative physiological stability despite moderate histological changes under TC. In contrast, salinity 40 caused severe cellular damage, including membrane remodeling, lipid peroxidation, depleted antioxidants, and neurotoxic responses. The integrated multi-level analysis revealed coordinated stress responses involving oxidative stress, altered energy metabolism, and detoxification. Overall, these findings highlight salinity 30 as the optimal condition for M. galloprovincialis and emphasize the synergistic effects of climate-driven salinity changes and antibiotic pollution, underscoring the need to account for abiotic stressors in ecotoxicological assessments.
{"title":"From metabolites to tissues: A comprehensive analysis of salinity-driven modulation of tetracycline effects in Mytilus galloprovincialis","authors":"Marta Cunha , Alessio Lenzi , Constança Figueiredo , Lucia De Marchi , Carla Leite , Tania Russo , Gianfranca Monni , Valentina Meucci , Amadeu M.V.M. Soares , Gianluca Polese , Eduarda Pereira , Carlo Pretti , Rosa Freitas","doi":"10.1016/j.cbpc.2025.110383","DOIUrl":"10.1016/j.cbpc.2025.110383","url":null,"abstract":"<div><div>Environmental salinity shifts, intensified by climate change, can influence the toxicity of pollutants such as antibiotics in marine organisms. In this study, specimens of the mussel <em>Mytilus galloprovincialis</em> were exposed for 28 days to three salinity levels (20, 30, and 40) in the presence or absence of tetracycline (TC) (1 mg/L). At the end of the exposure period, the effects were evaluated using an integrated metabolomic, biochemical, and histopathological approach. Tetracycline bioaccumulation did not differ significantly across salinities, indicating that biological effects were driven by stressor interactions rather than uptake. Metabolomic profiling showed that salinity and salinity-TC combinations had stronger impacts than TC alone. At salinity 20, mussels exhibited early oxidative stress and metabolic adjustments, along with tissue atrophy and lipofuscin buildup. Mussels at salinity 30 displayed relative physiological stability despite moderate histological changes under TC. In contrast, salinity 40 caused severe cellular damage, including membrane remodeling, lipid peroxidation, depleted antioxidants, and neurotoxic responses. The integrated multi-level analysis revealed coordinated stress responses involving oxidative stress, altered energy metabolism, and detoxification. Overall, these findings highlight salinity 30 as the optimal condition for <em>M. galloprovincialis</em> and emphasize the synergistic effects of climate-driven salinity changes and antibiotic pollution, underscoring the need to account for abiotic stressors in ecotoxicological assessments.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"300 ","pages":"Article 110383"},"PeriodicalIF":4.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145457878","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 : 2026-02-01Epub Date: 2025-11-29DOI: 10.1016/j.cbpc.2025.110418
Katie A. Edwards , Dennis Kleiner , Banshika M. Mangal , Bhavna S. Sonare
Thiamine (vitamin B1) deficiency is causative of reproductive failures and population declines in lake trout, Atlantic salmon, and other predatory fish species. Transketolase (TKT) is the rate-limiting enzyme of the non-oxidative phase of the pentose-phosphate pathway. TKT is critical for mediating the availability of sugars to return to glycolysis and for synthesizing NADPH and R5P, which are needed to maintain the cellular oxidation state and to produce biomolecules necessary for successful growth and reproduction. TKT activity provides a measure of functional thiamine availability since it requires thiamine diphosphate (TDP) as a coenzyme. Its activity is usually analyzed via a coupled enzyme reaction, including ribose-5-phosphate (R5P) and xylulose-5-phosphate (X5P) as substrates to permit the kinetic monitoring of the depletion of exogenous NADH. We developed a simplified, cost-effective procedure for quantifying TKT activity in fish liver to probe thiamine utilization and magnesium (Mg2+) dependence. Unlike previous protocols, the method omits costly X5P, relying instead on endogenous enzyme activity for in situ substrate generation. In two lake trout strains, TKT-specific activity correlated with TDP concentration while maximal activity reflected enzyme abundance and holoenzyme stability. By running samples with and without Mg2+ and over a range of TDP concentrations, the assay framework allows for distinguishing a Mg2+ limitation from a thiamine limitation and defines apparent EC50 and Vmax values. This simplified and tunable assay provides a tool for evaluation of thiamine-related metabolic resistance under dietary or environmental stress across fish populations and species.
{"title":"An updated transketolase activity assay to probe thiamine utilization in fish","authors":"Katie A. Edwards , Dennis Kleiner , Banshika M. Mangal , Bhavna S. Sonare","doi":"10.1016/j.cbpc.2025.110418","DOIUrl":"10.1016/j.cbpc.2025.110418","url":null,"abstract":"<div><div>Thiamine (vitamin B1) deficiency is causative of reproductive failures and population declines in lake trout, Atlantic salmon, and other predatory fish species. Transketolase (TKT) is the rate-limiting enzyme of the non-oxidative phase of the pentose-phosphate pathway. TKT is critical for mediating the availability of sugars to return to glycolysis and for synthesizing NADPH and R5P, which are needed to maintain the cellular oxidation state and to produce biomolecules necessary for successful growth and reproduction. TKT activity provides a measure of functional thiamine availability since it requires thiamine diphosphate (TDP) as a coenzyme. Its activity is usually analyzed via a coupled enzyme reaction, including ribose-5-phosphate (R5P) and xylulose-5-phosphate (X5P) as substrates to permit the kinetic monitoring of the depletion of exogenous NADH. We developed a simplified, cost-effective procedure for quantifying TKT activity in fish liver to probe thiamine utilization and magnesium (Mg<sup>2+</sup>) dependence. Unlike previous protocols, the method omits costly X5P, relying instead on endogenous enzyme activity for in situ substrate generation. In two lake trout strains, TKT-specific activity correlated with TDP concentration while maximal activity reflected enzyme abundance and holoenzyme stability. By running samples with and without Mg<sup>2+</sup> and over a range of TDP concentrations, the assay framework allows for distinguishing a Mg<sup>2+</sup> limitation from a thiamine limitation and defines apparent <em>EC</em><sub><em>50</em></sub> and <em>V</em><sub><em>max</em></sub> values. This simplified and tunable assay provides a tool for evaluation of thiamine-related metabolic resistance under dietary or environmental stress across fish populations and species.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"300 ","pages":"Article 110418"},"PeriodicalIF":4.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145647480","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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