Comparative Biochemistry and Physiology C-toxicology & Pharmacology最新文献

{"title":"Chronic copper exposure induces multi-systemic toxicity in Japanese medaka (Oryzias latipes) via reproductive disruption, and gut microbiota dysbiosis","authors":"Abdul Haleem Khan ,&nbsp;Muhammad Jawad ,&nbsp;Sana Nasir ,&nbsp;Haijing Xu ,&nbsp;Mengzhou Wu ,&nbsp;Junqiang Qiu ,&nbsp;Mingyou Li","doi":"10.1016/j.cbpc.2025.110402","DOIUrl":"10.1016/j.cbpc.2025.110402","url":null,"abstract":"<div><div>Copper (Cu²⁺), though essential as a micronutrient, can pose significant ecotoxicological risks when introduced into aquatic environments at elevated levels, primarily due to anthropogenic sources such as industrial discharge, agricultural runoff, and urban effluents. This study investigated the long-term effects of environmentally relevant copper concentrations (0, 5, 10, and 20 μg/L) on Japanese medaka (<em>Oryzias latipes</em>) over a six-month exposure period, focusing on reproductive toxicity, oxidative stress, immune response, and gut microbiota alterations. Histopathological analysis revealed gonadal impairments, including disrupted testicular and ovarian structures, impaired spermatogenesis, and reduced oocyte maturation. Additionally, hormonal changes revealed elevated levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol (E2), alongside reduced testosterone (T) levels, indicating interference with the hypothalamic–pituitary–gonadal (HPG) axis. Copper exposure also altered antioxidant enzyme activities, including sex-dependent modulation of superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) levels, indicating oxidative imbalance and compensatory defense responses, along with upregulation of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α). Gut microbiota analysis via 16S rRNA sequencing revealed significant dysbiosis, characterized by marked reductions in alpha diversity indices and distinct beta diversity clustering. Taxonomic profiling showed a sharp decline in beneficial phyla such as Fusobacteriota, Firmicutes, and Actinobacteriota, coupled with an enrichment of potentially opportunistic <em>Proteobacteria</em> and shifts in <em>Bacteroidota</em> and <em>Verrucomicrobiota</em>, indicating compromised intestinal homeostasis. Collectively, these findings demonstrate that chronic exposure to copper ions induces multi-systemic toxicity in <em>O. latipes</em>, impairing reproductive function, provoking oxidative and inflammatory responses, and reshaping gut microbial communities in ways that may exacerbate host physiological stress.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"300 ","pages":"Article 110402"},"PeriodicalIF":4.3,"publicationDate":"2025-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145602794","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}

{"title":"Sex-specific effects of 6PPD on adult zebrafish: male-selective feeding inhibition, nutrient malabsorption, intestinal epithelial damage, and absence of reproductive toxicity","authors":"Yuanhua Wang ,&nbsp;Jie Ren ,&nbsp;Siling Zhang ,&nbsp;Hao Xu","doi":"10.1016/j.cbpc.2025.110403","DOIUrl":"10.1016/j.cbpc.2025.110403","url":null,"abstract":"<div><div>The tire-derived antioxidant 6PPD (N-(1,3-dimethylbutyl)-<em>N</em>′-phenyl-<em>p</em>-phenylenediamine), a ubiquitous environmental contaminant, poses significant risks to aquatic ecosystems, yet its sex-specific physiological impacts remain underexplored. This study investigated the effects of environmentally relevant 6PPD concentrations (20 μg/L) on feeding, digestion, absorption, and reproduction in adult zebrafish over 28 days. Results revealed pronounced male-specific impairments: 6PPD-exposed males exhibited reduced feeding speed and maximum food intake, alongside suppressed locomotor responses to food stimuli. Mechanistically, upregulation of intestinal cholecystokinin b (<em>cckb</em>) and delayed intestinal content emptying were identified as potential drivers of feeding inhibition in males. Concurrently, 6PPD induced intestinal oxidative stress in males, manifested through decreased activities of catalase (CAT) and superoxide dismutase (SOD), alongside elevated malondialdehyde (MDA) levels, and activated ferroptosis via dysregulation of critical genes (<em>gpx4a</em>, <em>cybb</em>, <em>slc7a11</em>, <em>hmox1a</em>, <em>tfr1b</em> and <em>trf2</em>). These disruptions correlated with shortened intestinal villi, goblet cell loss, and impaired nutrient absorption, leading to increased fecal output and diminished growth performance in males. In contrast, females displayed no significant structural damage to intestinal epithelium or declines in digestive and absorptive capacities. Notably, 6PPD caused no gonadal histopathological changes, hormonal dysregulation, reduced fertilization and hatching rates, nor transgenerational effects such as developmental abnormalities or locomotor deficits in offspring. This study provides the first evidence of male-selective feeding suppression and intestinal toxicity induced by 6PPD, highlighting sex-dependent vulnerability in aquatic species and underscoring the need for gender-specific risk assessments of tire-derived pollutants.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"300 ","pages":"Article 110403"},"PeriodicalIF":4.3,"publicationDate":"2025-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145602782","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}

{"title":"Effects of taurine on immunity and ammonia metabolism in large-scale loach under ammonia stress","authors":"Ruo-Yu Zhou ,&nbsp;Lu Chen ,&nbsp;Meng-Yang Hu,&nbsp;Mu-Xi Li,&nbsp;Yu-Xuan Fei,&nbsp;Mei Huang,&nbsp;Yun-Long Zhang","doi":"10.1016/j.cbpc.2025.110395","DOIUrl":"10.1016/j.cbpc.2025.110395","url":null,"abstract":"<div><div>Ammonia is a common environmental pollutant that is extremely toxic to aquatic animals. Therefore, there is an urgent need to increase ammonia tolerance in aquaculture animals to achieve high-quality development of the industry. Three treatments were designed to examine the effects of taurine on the large-scale loach (<em>Paramisgurnus dabryanus</em>). These were a control group (exposed to water and injected with physiological saline), an ammonia treatment group (exposed to 30 mmol/L NH₄Cl solution and injected with physiological saline), and a taurine treatment group (exposed to 30 mmol/L NH₄Cl solution and injected with taurine). Immune- and ammonia metabolism-related markers were measured at 12 h, 24 h, 48 h, and 96 h after treatment. The results showed that ammonia exposure significantly increased T-SOD activity and the level of IL-1β, significantly decreased IgM, C3, and TNF-α levels, and induced significantly high expression of immune-related genes (<em>lyz</em>, <em>hsp70</em>, <em>tlr5</em>, and <em>myd88</em>) in tissues. Intraperitoneal injection of taurine mitigated ammonia-induced disturbances in plasma glucose and osmotic pressure by regulating glucose metabolism and osmotic pressure balance. The results suggest that ammonia stress causes significant immune stimulation in large-scale loaches, and that taurine could alleviate this effect. Exposure to ammonia increases the concentration of ammonia in the gut, liver, kidneys, and gills of large-scale loach, significantly increases GDH and GS activity, and upregulates the expression levels of ammonia transporter-related genes such as <em>aqps</em> and <em>rh</em>. After taurine treatment, the concentration of ammonia in the somatic tissues of large-scale loaches significantly decreased, while the expression of ammonia transporter-related genes was inhibited, and the activities of GS was further enhanced. This indicates that large-scale loach initiate glutamine synthesis and upregulate ammonia transporter proteins to cope with the stress of highly concentrated ammonia, and that taurine can promote glutamine synthesis to decrease the in vivo ammonia concentration. The results can deepen our understanding of the toxicological effects of ammonia and the mechanisms by which taurine promotes ammonia tolerance in fishes, offering a basis for taurine application in aquaculture.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"300 ","pages":"Article 110395"},"PeriodicalIF":4.3,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145596069","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}

{"title":"Acute toxicity assessment and real-time metabolic rate responses of early life stage Macrobrachium rosenbergii to ammonia exposures at different salinities","authors":"Cameron M. Emadi ,&nbsp;Fabio Dos Santos Neto ,&nbsp;Jason R. Bohenek ,&nbsp;Breana Smithers ,&nbsp;Miguel F. Acevedo ,&nbsp;Edward M. Mager","doi":"10.1016/j.cbpc.2025.110401","DOIUrl":"10.1016/j.cbpc.2025.110401","url":null,"abstract":"<div><div><em>Macrobrachium rosenbergii</em>, the giant freshwater prawn, is an important aquaculture species cultivated worldwide. As a catadromous species, it requires brackish water for early development (larval stages) and grows optimally under low-salinity conditions. This tolerance enables production using brackish groundwater or desalination concentrate, helping reduce disposal costs. However, aquaculture systems often accumulate nitrogenous waste such as ammonia, which can negatively affect growth, survival, and health. The interactive effects of ammonia and salinity on <em>M. rosenbergii</em> remained understudied, particularly during juvenile stages that coincide with the transition to brackish water. Therefore, we first determined the 3, 6, 24, and 48 h median lethal concentrations (LC₅₀) of total ammonia nitrogen (TAN) across three salinities (1, 5, and 10 ppt) at pH 8.2. Toxicity increased with both salinity and exposure time, with LC₅₀ values ranging from 5.6 mg/L (95 % CI: 4.9–6.3) to 42 mg/L (95 % CI: 37–48) TAN. Based on these LC₅₀ values, we tested how increasing waterborne ammonia concentrations affect the routine metabolic rate (RMR) of juvenile <em>M. rosenbergii</em> using static intermittent respirometry. Analysis by a linear mixed-effects model revealed a significant salinity × ammonia interaction where the positive relationship between ammonia concentration and RMR became steeper at higher salinities. The model also identified a significant main effect of ammonia, with RMR increasing as ammonia concentration rose, but no significant main effect of salinity. These findings inform aquaculture management of <em>M. rosenbergii</em> and demonstrate the potential for sentinel respirometry systems to detect real-time water quality changes by monitoring metabolic rates.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"300 ","pages":"Article 110401"},"PeriodicalIF":4.3,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145596032","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}

{"title":"The marine water flea Diaphanosoma celebensis as an emerging model for ocean health research: A review","authors":"Duck-Hyun Kim ,&nbsp;Jin-Sol Lee ,&nbsp;Min-Sub Kim ,&nbsp;Zhou Yang ,&nbsp;Atsushi Hagiwara ,&nbsp;Jae-Seong Lee","doi":"10.1016/j.cbpc.2025.110400","DOIUrl":"10.1016/j.cbpc.2025.110400","url":null,"abstract":"<div><div><em>Diaphanosoma celebensis</em>, a marine water flea, has gained recognition as a valuable model organism in marine ecotoxicology, ecophysiology, and epigenetics. This review highlights the significance of <em>D. celebensis</em> in environmental research, emphasizing its high-quality genomic and transcriptomic resources, adaptability to environmental stressors, and sensitivity to pollutants. The species' utility in studying molecular responses to contaminants such as microplastics, heavy metals, and endocrine disruptors is underscored by its ability to provide insights into detoxification pathways, stress response mechanisms, and epigenetic modifications. <em>Diaphanosoma celebensis</em> serves as a critical tool for advancing our understanding of the ecological impacts of pollution and the adaptive capacities of marine invertebrates. This review synthesizes existing research, explores the species' strengths as a research model, and identifies future research directions. All evidence suggests <em>D. celebensis</em> can complement traditional freshwater models and enhance our capacity to monitor and protect marine health.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"300 ","pages":"Article 110400"},"PeriodicalIF":4.3,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145581979","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}

{"title":"Rare earth element lanthanum induces inflammatory response in zebrafish through TLR4/NF-κB signaling pathway","authors":"Xinhao Ye ,&nbsp;Shiyi Duan ,&nbsp;Hao Wang ,&nbsp;Shimei Xiao ,&nbsp;Mijia Li ,&nbsp;Wei Yuan ,&nbsp;Yan Zhao ,&nbsp;Yiyue Zhang ,&nbsp;Keyuan Zhong","doi":"10.1016/j.cbpc.2025.110391","DOIUrl":"10.1016/j.cbpc.2025.110391","url":null,"abstract":"<div><div>The inflammatory response is a core protective physiological process against stimuli like infection or injury, and can be initiated by autoimmune disorders. It is primarily characterized by neutrophil-dominated leukocytosis and may lead to multiple organ dysfunction in severe cases. Environmental factors play an important role in the inflammatory response. Rare earth elements are not essential elements for living organisms. However, owing to large-scale mining and use, their concentrations in the environment have increased. Thus, rare earth elements are now considered emerging environmental pollutants, and the risks that rare earth elements pose to human health need further investigation. In this study, zebrafish were used as experimental animals, and zebrafish embryos were exposed to the different concentrations of lanthanum chloride (0, 5, 15, and 25 mg/L) to analyze its effect on embryo development and immune system. The number and distribution of zebrafish neutrophils as well as changes in oxidative stress and the expression of genes related to inflammation were analyzed. The results indicated that lanthanum chloride exposure reduced the heart rate, shortened the body length, and increased the yolk area of zebrafish embryos. In addition, exposure to lanthanum chloride caused the diffusion of neutrophils, leading to inflammation in zebrafish. Concurrently, the exposure led to the accumulation of reactive oxygen species in zebrafish, which subsequently resulted in the upregulation of malondialdehyde, catalase, and superoxide dismutase levels. Further experiments revealed that exposure to lanthanum chloride led to the upregulation of several inflammation-related genes, such as <em>il-6</em>, <em>il-8</em>, <em>il-10</em>, and <em>cxcl-c1c</em>, as well as certain TLR4/NF-κB signaling-related genes, including <em>tlr4</em>, <em>myd88</em>, <em>nf-κb p65</em>, <em>il-1β</em>, and <em>tnf-α</em>. The TLR4/NF-κB signaling pathway inhibitor andrographolide can alleviate the inflammatory response induced by lanthanum chloride exposure. In conclusion, lanthanum chloride induced inflammation in zebrafish by activating the TLR4/NF-κB signaling pathway. The study results can provide a reference for evaluating the health risks of rare earth elements in humans.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"300 ","pages":"Article 110391"},"PeriodicalIF":4.3,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145581934","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}

{"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}

{"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 ,&nbsp;Wangta Liu ,&nbsp;Pei-Hsuan Chen ,&nbsp;Chia C. Wang ,&nbsp;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}

{"title":"Polystyrene microplastics and nanoplastics induce neurotoxicity in zebrafish via oxidative stress and neurotransmitter disruption","authors":"Jiejie Li ,&nbsp;Yingjie Chen ,&nbsp;Yuequn Chen ,&nbsp;Han Xie ,&nbsp;Ganglong Wu ,&nbsp;Yiming Zhang ,&nbsp;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}

{"title":"Developmental hepatotoxicity induced by flusilazole in zebrafish: Mechanistic insights into mitochondrial dysfunction, oxidative stress, ferroptosis, and regenerative impairment","authors":"Hojun Lee ,&nbsp;Jisoo Song ,&nbsp;Garam An ,&nbsp;Seung-Min Bae ,&nbsp;Gwonhwa Song ,&nbsp;Whasun Lim ,&nbsp;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}