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

{"title":"Mixture predicted no-effect concentrations of surfactants and antibiotics: Modeling based on experimental testing","authors":"Zi-Yi Zheng,&nbsp;Jing-Xuan Zhou,&nbsp;Xiong-Bo Liu,&nbsp;Si-Yu Li,&nbsp;Hong-Gang Ni","doi":"10.1016/j.cbpc.2025.110335","DOIUrl":"10.1016/j.cbpc.2025.110335","url":null,"abstract":"<div><div>Environmental transport pathways of antibiotics resemble those of surfactants, and the two often co-exist in aqueous environments, represent a significant ecological risk. Although the individual toxicities of these chemicals are well-documented, their combined effects and the corresponding mixture predicted no-effect concentrations (PNECs) have not been adequately investigated. This study examined the combined toxicity of fluoroquinolone antibiotics (levofloxacin (LEV) and enrofloxacin (ENR)) and nonionic surfactant (octylphenol ethoxylate (TritonX-100)) through acute toxicity tests on <em>Daphnia magna</em>, a widely used model organism for freshwater toxicity assessment due to its high sensitivity to pollutants and ecological relevance. The concentration addition and independent action models were used to assess the combined toxicity interactions, while the interspecies correlation estimation (ICE) and species sensitivity distribution (SSD) models were employed to estimate the mixture PNECs of surfactants and antibiotics at different mixing ratios. The results indicated that synergistic effects were observed in both sets of binary mixtures. The differences of PNECs caused by varying mixing ratios within the same mixture system were as high as 24.7 %, with values ranging from 260.73 to 325.23 μg/L for the Triton X-100–LEV and from 247.85 to 284.57 μg/L for the Triton X-100–ENR. The study highlights the importance of mixture effects in ecological risk assessments, as ignoring these factors may lead to inaccurate predictions of environmental risks.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"298 ","pages":"Article 110335"},"PeriodicalIF":4.3,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144921532","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":"Transcriptomic profiling reveals tetrabromobisphenol A-induced dysregulation of hepatic lipid homeostasis in common carp (Cyprinus carpio)","authors":"Yimin Li ,&nbsp;Chunnuan Zhang ,&nbsp;Zihao Meng ,&nbsp;Mengkang You ,&nbsp;Huajuan Shi","doi":"10.1016/j.cbpc.2025.110336","DOIUrl":"10.1016/j.cbpc.2025.110336","url":null,"abstract":"<div><div>TBBPA, a ubiquitously distributed brominated flame retardant, poses significant ecological risks due to its bioaccumulative potential and toxicity. Previous investigations have predominantly focused on untargeted metabolomics and lipidomics to characterize the effects of TBBPA on metabolic end products. However, limited data are available regarding the mechanisms underlying TBBPA-induced disruption of lipid metabolism in aquatic organisms. This study systematically investigated the dose-dependent effects of TBBPA on lipid metabolism in common carp through integrated biochemical, histochemical evaluations, and transcriptomic profiling. Fish were exposed to environmentally relevant TBBPA concentrations (0, 0.005, 0.05, and 0.5 mg/L) for a 14-day duration. Serum biochemical analyses revealed dose-dependent hyperlipidemia, manifested by elevated TG and T-CHO levels, suppressed SOD and CAT activities, and increased MDA levels. Oil Red O staining demonstrated hepatic lipid droplet accumulation despite no significant (<em>P</em> &gt; 0.05) alterations in intrahepatic TG/T-CHO content, with the 0.5 mg/L group exhibited the most severe histopathological phenotype. Transcriptomic profiling identified the AMPK and PPAR signaling pathways as pivotal regulators of TBBPA-induced metabolic dysregulation. Under low-dose TBBPA exposure (0.05 mg/L), lipid accumulation triggered compensatory activation of the <em>AMPK</em>/<em>PPAR-α</em>/<em>CPT1</em> axis, enhancing fatty acid β-oxidation to partially counteract lipid deposition. Conversely, high-dose TBBPA (0.5 mg/L) disrupted lipid metabolism through coordinated upregulation of genes associated with lipid synthesis, transport, and storage, culminating in pathological lipid deposition. This study provides critical insights into the molecular cascades underlying TBBPA-induced metabolic dysregulation in aquatic species, highlights the dose-dependent disruption of lipid homeostasis.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"299 ","pages":"Article 110336"},"PeriodicalIF":4.3,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945506","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":"GW-9662, a peroxisome proliferator-activated receptor γ (PPARγ) inhibitor, impairs early embryonic development in zebrafish","authors":"Sunil Sharma ,&nbsp;Kanchaka Senarath Pathirajage ,&nbsp;Tyler Johnson ,&nbsp;Jabez Raju Battu ,&nbsp;Subham Dasgupta","doi":"10.1016/j.cbpc.2025.110332","DOIUrl":"10.1016/j.cbpc.2025.110332","url":null,"abstract":"<div><div>Peroxisome proliferator-activated receptor γ (PPARγ) functions as a nuclear transcription factor with primary roles in lipid and glucose metabolism and adipocyte differentiation. Despite intensive research in metabolic contexts, its role during early vertebrate development remains underexplored. Our study focused on understanding PPARγ's developmental role by using a PPARγ antagonist, GW-9662 (GW), in zebrafish embryos. We exposed embryos to GW from 6 hours post-fertilization (hpf) to 24 hpf and observed that the embryos were ventralized by 24 hpf. Western Blot and immunohistochemistry for PPARγ protein demonstrated that GW-mediated PPARγ inhibition may be localized within the embryos. Transcriptomic analysis revealed that exposure to GW led to dysregulation of multiple biological pathways, including cytoskeletal organization, lipid biosynthesis, and epithelial-to-mesenchymal transition (EMT). Immunohistochemistry further validated these findings, demonstrating increased lipid accumulation, cytoskeletal disruption, and altered EMT markers. Our findings suggest that while GW plays a crucial role in multiple physiological processes during early embryogenesis, further research is needed to examine if these impacts are mediated by PPARγ.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"298 ","pages":"Article 110332"},"PeriodicalIF":4.3,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144907913","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":"Collateral damage of neonicotinoid insecticides: Unintended effects on gut microbiota of non-target organisms","authors":"Muhammad Nadeem Khan ,&nbsp;Hazrat Bilal ,&nbsp;Sabir Khan ,&nbsp;Muhammad Shafiq ,&nbsp;Xiaoyang Jiao","doi":"10.1016/j.cbpc.2025.110330","DOIUrl":"10.1016/j.cbpc.2025.110330","url":null,"abstract":"<div><div>Neonicotinoids (NEOs) are widely used insecticides known for their effectiveness in pest control. However, concerns have emerged regarding their persistence in the environment and unintended effects on non-target organisms, particularly gut microbiota. The gut microbiota, essential for digestion, immunity, and metabolic health, can be disrupted by NEOs, leading to dysbiosis, immune dysfunction, metabolic disturbances, and increased susceptibility to infections. NEO exposure has been shown to reduce microbial diversity, particularly beneficial bacteria, in species like honeybees, rodents, and humans. This disruption can contribute to conditions such as inflammation, gastrointestinal disorders, and systemic diseases. This review compares the effects of various NEOs, including imidacloprid, thiamethoxam, and clothianidin, on gut microbiota across species. It highlights the detrimental impact on microbial communities, particularly in pollinators like bees, and extends to vertebrates and aquatic organisms. The disruption of gut microbiota can lead to severe ecological consequences, including impaired pollination, reduced plant health, and compromised ecosystem resilience. There is an urgent need for further research to understand the mechanisms behind NEO-induced microbiota disruption and to develop sustainable pest management alternatives. It advocates for stricter regulations, the development of biopesticides, and the use of probiotics to mitigate gut microbiota disruption. Addressing these issues through comprehensive studies and regulatory measures is crucial to protect non-target organisms, ecosystems, and public health from the unintended collateral damage of NEOs.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"298 ","pages":"Article 110330"},"PeriodicalIF":4.3,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144865162","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":"Proteomic responses to acute sesamolin exposure in zebrafish embryos","authors":"Wannakarn Kitipaspallop ,&nbsp;Sittiruk Roytrakul ,&nbsp;Chanpen Chanchao ,&nbsp;Wittaya Pimtong","doi":"10.1016/j.cbpc.2025.110322","DOIUrl":"10.1016/j.cbpc.2025.110322","url":null,"abstract":"<div><div>Sesamolin, a lignan with known pharmacological benefits, has been extensively studied for its neuroprotective, antioxidative, and anticancer properties. This study builds upon previous investigations into the acute toxicity of sesamolin, presenting a detailed examination of its effects on zebrafish embryonic development through a proteomic approach. Zebrafish embryos were exposed to 25 and 50 μM concentrations of sesamolin for 72 h, resulting in significant developmental abnormalities, including yolk sac edema, spinal curvature, blood clots, and defects in erythropoiesis. Proteomic analysis revealed a dose-dependent downregulation of 162 proteins, including vital clusters such as vitellogenins, ribosomal proteins, cytoskeletal proteins, heat shock proteins, hemoglobin proteins, and ATP synthase. These alterations are linked to disrupted protein synthesis, impaired structural integrity, energy production deficits, and abnormal embryonic nutrient utilization. The study suggests that sesamolin exerts its toxic effects by interfering with key molecular mechanisms essential for normal embryogenesis, specifically affecting protein expression involved in development, cell structure, and metabolic processes. These findings provide novel insights into the potential adverse effects of sesamolin on embryonic development and highlight the need for further research to elucidate the underlying molecular pathways and assess the compound's broader toxicological risks, particularly in relation to human health.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"298 ","pages":"Article 110322"},"PeriodicalIF":4.3,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144865163","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":"Microcystin-LR hijacks mitochondrial bioenergetics and Wnt crosstalk: Unveiling a novel dual-pathway mechanism for adipogenesis dysregulation in environmental toxicology","authors":"Wenqi Duan ,&nbsp;Tian Yang ,&nbsp;Wanjing Liu ,&nbsp;Chunhua Zhan","doi":"10.1016/j.cbpc.2025.110329","DOIUrl":"10.1016/j.cbpc.2025.110329","url":null,"abstract":"<div><div>Cyanobacterial blooms, driven by toxin-producing cyanobacteria, pose significant environmental health risks due to the persistent release of cyanotoxins like microcystin-LR (MC-LR). While much research has focused on its hepatotoxic, nephrotoxic, and neurotoxic effects, its impact on adipose tissue homeostasis remains poorly understood. This study investigates the effects of MC-LR on stromal vascular fraction (SVF) cells, key progenitors in adipogenesis and metabolic regulation. Using cell culture models, we examine mitochondrial dysfunction and Wnt/β-catenin signaling pathway as two primary mechanisms of MC-LR-induced adipose dysfunction. Our findings show that MC-LR exposure leads to ATP depletion, ROS accumulation, impaired oxidative phosphorylation, and mitophagy activation, which collectively suppress lipogenesis. Additionally, MC-LR activates Wnt/β-catenin signaling pathway, disrupting adipogenesis regulatory pathways. These mechanisms interact in a self-reinforcing cycle of adipocyte dysfunction, linking mitochondrial failure to Wnt/β-catenin pathway hyperactivation. This study is the first to systematically elucidate the molecular mechanisms by which MC-LR disrupts adipogenesis in SVF cells, providing critical insights into the role of cyanotoxins in modulating human adipogenesis and obesity-related metabolic dysregulation.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"298 ","pages":"Article 110329"},"PeriodicalIF":4.3,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862186","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":"Comparative analyses of venom and salivary gland-specific anti-microbial peptide and proteins of some hymenopteran and heteropteran insects","authors":"Jong Hyeok Lee ,&nbsp;Woo-Jin Kim ,&nbsp;Yue Gao ,&nbsp;Neung-Ho Ahn ,&nbsp;Won-Jae Chi ,&nbsp;Jong-Hoon Kim ,&nbsp;Si Hyeock Lee ,&nbsp;Kyungjae Andrew Yoon","doi":"10.1016/j.cbpc.2025.110326","DOIUrl":"10.1016/j.cbpc.2025.110326","url":null,"abstract":"<div><div>To test the hypothesis that the expression profiles, evolutionary patterns, and functionalities of anti-microbial peptides (AMPs) and proteins in some hymenopteran and heteropteran species are influenced by their distinct ecological traits, we conducted venom and salivary gland-specific transcriptome analyses. We compared the expression and evolutionary patterns of anti-microbial peptide and proteins across 22 hymenopteran and 9 heteropteran species. Additionally, we investigated the structural properties of selected defensins and assessed their anti-microbial and hemolytic activities. Defensin expression in social wasps from the family Vespidae was higher than that from the family Apidae and in solitary hunting wasps. Among heteropterans, only 2 species <em>C. lectularius</em> and <em>G. rubrolineatum</em> showed higher transcript levels than any others examined. Notably, the social wasp <em>V. flaviceps</em> and the phytophagous heteropteran <em>G. rubrolineatum</em> exhibited the highest levels of defensin expression among the hymenopteran and heteropteran species studied, respectively. Most anti-microbial peptide and proteins, with the exception of peptidoglycan recognition protein-SC2 in hymenopteran species, exhibited evolutionary patterns that were distinct from the typical hymenopteran and heteropteran lineage structures. Among the defensins derived from hymenopteran and heteropteran species, as well as the traditional antibiotics tested, the defensin from the phytophagous heteropteran <em>G. rubrolineatum</em> exhibited the strongest Gram-positive bacteria-specific anti-microbial activity. These findings provide valuable insights into the evolutionary dynamics and functional diversity of hymenopteran and heteropteran anti-microbial peptide and proteins and may contribute to the development of novel AMP-based strategies as promising alternatives to conventional antibiotics.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"298 ","pages":"Article 110326"},"PeriodicalIF":4.3,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144842052","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":"Comparative toxicological impacts of tire wear and latex particle leachates on zebrafish embryos: Chemical characterization, oxidative stress, and transcriptomic disruption","authors":"Qianqian Song ,&nbsp;Qingxuan Meng ,&nbsp;Xinrui Meng ,&nbsp;Jin Chen ,&nbsp;Jing Cong","doi":"10.1016/j.cbpc.2025.110323","DOIUrl":"10.1016/j.cbpc.2025.110323","url":null,"abstract":"<div><div>Rubber-derived pollutants, such as tire wear particles (TWP) and latex particles (LAP), pose increasing threats to aquatic ecosystems due to their complex chemical composition and potential toxicity. This study systematically evaluated the embryotoxicity of 30-day leachates from TWP and LAP (10 g/L) in zebrafish (<em>Danio rerio</em>) by integrating chemical characterization and toxicological assessment. ICP-MS and GC–MS analyses revealed elevated levels of toxic metals, notably zinc and aluminum that exceeded established ambient water quality criteria for aquatic life, along with numerous organic contaminants including antioxidants, plasticizers, and accelerators. LAP leachates exhibited significantly greater toxicity than TWP, as indicated by a lower LC₅₀ (3.33 g/L), increased mortality and malformation rates, delayed percent hatched, and reductions in spontaneous movement, heartbeat, and body length. Oxidative stress biomarkers revealed disrupted antioxidant enzyme activity and elevated malondialdehyde (MDA) levels, particularly in the LAP group. Transcriptomic profiling revealed that both ferroptosis and arachidonic acid metabolism were commonly enriched pathways. Notably, LAP exposure induced broader alterations in metabolic and inflammatory processes, whereas TWP exposure primarily impacted stress and apoptosis-related pathways. RT-qPCR validation confirmed significant gene expression changes, including the downregulation of cardiac-related genes (<em>tnnt2d</em>, <em>stc1l</em>) and upregulation of oxidative stress and inflammation markers (<em>ptgs2b</em>, <em>mt2</em>). Collectively, these findings demonstrate the heightened embryotoxicity of LAP leachates and the divergent molecular responses elicited by TWP and LAP, underscoring the need for targeted environmental regulation and risk mitigation strategies.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"298 ","pages":"Article 110323"},"PeriodicalIF":4.3,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144842053","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":"Colchicine induces developmental defects and renal toxicity in zebrafish by upregulating the oxidative stress","authors":"Fang Chen ,&nbsp;Haiyan Wei ,&nbsp;Dalong Liao ,&nbsp;Yong Huang ,&nbsp;Yijian Chen ,&nbsp;Huiqiang Lu ,&nbsp;Rong Xu","doi":"10.1016/j.cbpc.2025.110328","DOIUrl":"10.1016/j.cbpc.2025.110328","url":null,"abstract":"<div><div>Colchicine is a type of alkaloid commonly used clinically for treating diseases such as gouty arthritis. Studies suggest that colchicine is toxic to the kidneys. However, the specific mechanisms are unclear. Herein, we used zebrafish to validate the renal toxicity of colchicine and investigate the underlying mechanisms. Zebrafish larvae at 3 days post-fertilization were exposed to various concentrations (15, 20, and 25 mg/L) of colchicine solution for 72 h. Results showed that colchicine caused death, slowed heart rate, slowed growth, increased interpupillary distance, caused periorbital and renal capsule edema, caused swelling of glomerular podocytes, and disrupted the development of distal convoluted tubules of renal tubules. ROS staining revealed that colchicine increased oxidative in the glomerular. Mature zebrafish adults were exposed to colchicine solution concentrations of 0.15 and 1.5 mg/L for 4 weeks. Hematoxylin eosin staining of the kidney showed that the glomerular podocyte structure was disordered, renal tubular nuclei were irregularly arranged, and cell density was reduced. A significant increase in oxidative stress kinase activity was observed. Additionally, there was abnormal expression of genes related to kidney development and function. Abnormalities in kidney injury biomarkers were also observed in zebrafish, including urea nitrogen (BUN), creatinine (CR), and β-<em>N</em>-acetylglucosaminidase (NAG). These findings suggest that colchicine induced developmental defects and caused renal toxicity in zebrafish. Interestingly, treatment with astaxanthin (ASTA) partially reversed the structural and physiological damage in the kidney. Conclusively, colchicine induces developmental and renal toxicity in zebrafish by upregulating oxidative stress.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"298 ","pages":"Article 110328"},"PeriodicalIF":4.3,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854775","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":"Zearalenone accelerates aging and mitochondrial dysfunction: Evidence from network toxicology and zebrafish models","authors":"Rong Li ,&nbsp;Ziyuan Zhang ,&nbsp;Yu Xu","doi":"10.1016/j.cbpc.2025.110325","DOIUrl":"10.1016/j.cbpc.2025.110325","url":null,"abstract":"<div><div>Zearalenone (ZEN), a ubiquitous mycotoxin contaminating cereals and feed, is best known for reproductive toxicity. It remains unclear whether chronic, low-level exposure contributes to aging and mitochondrial decline. Here, we combine network toxicology, molecular docking, transcriptomics and zebrafish (<em>Danio rerio</em>) models to address this question.</div><div>In silico analyses identified 30 high-confidence ZEN targets linked to aging or mitochondrial biology; AKT1, MAPK3, TP53 and NFKB1 emerged as the central hubs. Docking predicted strong binding affinities (−6.2 to −8.3 kcal/mol) and 100 ns molecular-dynamics simulations confirmed stable complex formation.</div><div>Translating these predictions to a living system, we exposed zebrafish larvae to 2 μM ZEN. Within 72 h this produced overt developmental toxicity (delayed hatching, bradycardia, skeletal malformations) and sarcopenia-like muscle degeneration. Transmission-electron microscopy revealed disorganised sarcomeres; immunostaining showed reduced myosin heavy-chain expression. Oxidative stress (DCF fluorescence) rose markedly, while ATP-synthase transcripts were down-regulated. Locomotor assays at 96 h revealed a selective loss of high-speed swimming bouts. RNA-seq corroborated dysregulation of MAPK, PI3K–AKT and apoptosis pathways; longevity-linked genes (igf1, sirt1, nfkb2) were significantly downregulated.</div><div>Collectively, our work provides the first integrated evidence that ZEN exposure accelerates organismal aging through mitochondrial dysfunction and suggests that tighter mycotoxin surveillance is warranted as populations grow older.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"298 ","pages":"Article 110325"},"PeriodicalIF":4.3,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144844822","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}