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

{"title":"Hepatic toxicity assessment of organophosphorus insecticide isazophos on zebrafish","authors":"Li Chen ,&nbsp;Feifeng Chen ,&nbsp;Jiahui Li ,&nbsp;Mijia Li ,&nbsp;Xiaoping Xiao ,&nbsp;Qiang Luo ,&nbsp;Guiyou Tian ,&nbsp;Weixin Zhang","doi":"10.1016/j.cbpc.2025.110324","DOIUrl":"10.1016/j.cbpc.2025.110324","url":null,"abstract":"<div><div>Isazophos, an organophosphorus insecticide, is a prevalent environmental contaminant that bioaccumulates in organisms and poses significant risks to human health. However, the organ toxicity of isazophos to aquatic organisms has not been previously characterized. The purpose of this study is to investigate the toxic effects of isazophos exposure on zabrafish liver, as well as revealing the underlying toxicological mechanisms. Acute and chronic toxicity assessments showed 72 h and 28 days lethal concentration (LC₅₀) values of 2.612 mg/L and 0.172 mg/L for zebrafish embryos and adult zebrafish, respectively. The level of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and inflammation related genes revealed that isazophos affects early zebrafish development and causes liver damage via reactive oxygen species (ROS)-induced oxidative stress and inflammatory with upregulated pro-inflammatory factors (<em>il-6</em>, <em>il-8</em>, <em>il-1β</em> and <em>TNF-α</em>). Moreover, when exposed to isazophos, the glycogen content of the liver was decreased, while lipid accumulation was increased, and liver metabolism-related indices were changed. The ratios of pro-apoptotic genes <em>p53</em>, <em>bax</em>/<em>bcl-2</em>, <em>caspase 9</em> and <em>caspase 3</em> were upregulated. And the caspase3 and cleaved-caspase3 protein expression was evaluated in the isazophos group, revealing that isazophos caused aptoptotic. In conclusion, isazophos induces oxidative stress through the production of ROS, leading to the activation of pathways associated with apoptosis. The present study provides a systematic analysis of isazophos-induced hepatic effects in zebrafish liver and demonstrates that exposure to isazophos affects normal hepatic metabolism.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"298 ","pages":"Article 110324"},"PeriodicalIF":4.3,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144844820","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":"Integrated untargeted metabolomics and physiological analysis reveal the response mechanisms of Procambarus clarkii larvae to carbonate alkalinity exposure","authors":"Kun Guo ,&nbsp;Zhigang Zhao ,&nbsp;Rui Zhang ,&nbsp;Liang Luo ,&nbsp;Shihui Wang ,&nbsp;Wei Xu","doi":"10.1016/j.cbpc.2025.110327","DOIUrl":"10.1016/j.cbpc.2025.110327","url":null,"abstract":"<div><div>High alkalinity stress represents a critical yet understudied threat to aquatic organisms in saline-alkaline ecosystems. This study provides the first comprehensive investigation of carbonate alkalinity tolerance mechanisms in larval <em>Procambarus clarkii</em>, employing an innovative dual-approach methodology. Two experiments were conducted: the first aimed to determine the semi-lethal concentration (LC₅₀) and safe concentration (SC) of alkalinity for larval <em>P. clarkii</em>, and the second to evaluate the physiological and biochemical enzyme activities and metabolic level under 96 h acute alkalinity stress. The LC₅₀ alkalinity values of larval <em>P. clarkii</em> at 24, 48, 72, and 96 h were 25.57, 21.43, 18.40 and 16.03 mmol/L, respectively. The results of biochemical and physiological analyses showed that alkalinity stress disrupted oxidative immune balance, and physiological metabolism leading to increased superoxide dismutase (SOD), alkaline phosphatase (AKP), acid phosphatase (ACP), Na⁺-K⁺-ATPase, succinate dehydrogenase (SDH), glutamine synthetase (GS), glutamate dehydrogenase (GLDH), glutamic pyruvic transaminase (GPT) and glutamic oxalacetic transaminase (GOT) activities and malondialdehyde (MDA) contents and decreased catalase (CAT) and glycogen activities. Metabolomics analysis showed that in comparison with the control group, 414 (70 up- and 344 downregulated) and 675 (67 up- and 608 downregulated) significantly differential metabolites were identified in the A6 and A12 experimental groups, respectively. Our findings suggest that <em>P. clarkii</em> possess a certain level of tolerance to alkalinity stress; however, exposure to high alkalinity stress can adversely affect the antioxidant defense system, energy metabolism and immune response of crayfish. Our integrated approach provides a new framework for assessing crustacean resilience to saline-alkaline stress, with direct implications for aquaculture management under climate change scenarios.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"298 ","pages":"Article 110327"},"PeriodicalIF":4.3,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144844821","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":"HFPO-TA induces liver damage and ferroptosis in zebrafish by disrupting iron metabolism homeostasis","authors":"Lin Cheng ,&nbsp;Zhonghua Fan ,&nbsp;Yu Zhang ,&nbsp;Xu Fang ,&nbsp;Yuanyuan Wu ,&nbsp;Hongru Liu ,&nbsp;Lanxi Ye ,&nbsp;Li Wang ,&nbsp;Hui Liu","doi":"10.1016/j.cbpc.2025.110318","DOIUrl":"10.1016/j.cbpc.2025.110318","url":null,"abstract":"<div><div>Hexafluoropropylene oxide trimeric acid (HFPO-TA) is a novel alternative to perfluorooctanoic acid (PFOA) with similar toxicity to PFOA. However, whether HFPO-TA causes ferroptosis is currently unknown. In this experiment, we systematically investigated the induction of zebrafish embryonic liver ferroptosis by HFPO-TA to cause liver injury. The liver morphology and the extent of inflammatory damage were then visualized by Sudan Black B and H&amp;E staining, as well as through observations of <em>Tg (fabp10a: DsRed)</em>, <em>Tg (lyz: DsRed)</em> and <em>Tg (Xla.Eef1a1: mlsEGFP)</em> transgenic zebrafish. Differentially expressed genes associated with ferroptosis were identified using transcriptomics data previously done in the lab, and from these, three were selected as receptors for molecular docking with HFPO-TA, and both receptors and ligands were able to dock successfully. We then observed zebrafish under the microscope using ROS, DPPP and FerroOrange staining, respectively. The expression of key genes was verified by RT-qPCR. The results showed that HFPO-TA could lead to a significant increase in the levels of ROS, lipid peroxides and divalent iron ions, liver inflammation and injury, and a trend of elevated differential genes such as <em>tfa</em> and <em>tfr1a</em>. We then validated the ferroptosis pathway using an agonist (RSL3) and an inhibitor (Fer-1), and found that the inhibitor was able to ameliorate HFPO-TA-induced inflammatory and ferroptosis responses, whereas the agonist did the opposite. In conclusion, the ability of HFPO-TA to induce ferroptosis, which leads to liver injury provides new insights into the mechanism of HFPO-TA toxicity.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"298 ","pages":"Article 110318"},"PeriodicalIF":4.3,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803824","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":"Overexpression of CYP6CY36 and CYP380C34 contributes to metabolic resistance of Myzus persicae (Sulzer) to flupyradifurone","authors":"Qiuling Tang ,&nbsp;Jinfeng Hu ,&nbsp;Chengfeng Zheng ,&nbsp;Wei Zhang ,&nbsp;Jie Bi ,&nbsp;Yanping He","doi":"10.1016/j.cbpc.2025.110317","DOIUrl":"10.1016/j.cbpc.2025.110317","url":null,"abstract":"<div><div>Flupyradifurone is a novel butenolide insecticide widely applied to control a broad range of sucking pests, including <em>Myzus persicae</em>. However, resistance monitoring has revealed that several Chinese populations have developed moderate resistance to flupyradifurone. Therefore, we investigated the risk and underlying mechanisms of flupyradifurone resistance in <em>M. persicae</em>. A flupyradifurone-resistant strain (FDF-R) was established through 14 generations of selection and exhibited a 35.02-fold increase in resistance. FDF-R showed cross-resistance to acetamiprid (13.9-fold), sulfoxaflor (3.5-fold), and imidacloprid (4.2-fold), but not to tested pyrethroid or carbamate insecticides. The synergist piperonyl butoxide significantly increased flupyradifurone toxicity in FDF-R, suggesting the involvement of cytochrome P450 monooxygenases, whereas the other two synergists had no effect. Enzyme assays revealed 1.74-fold higher P450 activity in FDF-R compared to the susceptible strain. Gene expression analysis showed significant overexpression of seven P450 genes, including <em>CYP380C34</em>, <em>CYP6CY36</em>, <em>CYP6CY4</em>, and <em>CYP6CY3</em>. Moreover, RNAi silencing of <em>CYP6CY36</em> and <em>CYP380C34</em> significantly increased susceptibility to flupyradifurone. Additionally, molecular docking further confirmed strong binding affinities between these two P450 enzymes and flupyradifurone. These findings demonstrate that P450-mediated detoxification contributes to <em>M. persicae</em> resistance to flupyradifurone.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"298 ","pages":"Article 110317"},"PeriodicalIF":4.3,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144779716","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":"Cadmium exposure improved the susceptibility of wolf spider Pardosa pseudoannulata to pathogen","authors":"Juan Wang ,&nbsp;Yingying Lu ,&nbsp;Xinyi Wu ,&nbsp;Xinru Zhang ,&nbsp;Bo Lv ,&nbsp;Zhi Wang","doi":"10.1016/j.cbpc.2025.110307","DOIUrl":"10.1016/j.cbpc.2025.110307","url":null,"abstract":"<div><div>The farmland soil polluted by heavy metals like cadmium (Cd) was widespread around the world. Cd pollution may pose significant challenges to paddy arthropods by compromising their ability to resist infections from parasites and pathogens. This study investigated the impact of Cd exposure on the resistance of the <em>Pardosa pseudoannulata</em> against the pathogenic bacterium <em>Staphylococcus aureus</em>. Ecotoxicology assay suggested that Cd exposure significantly reduced the spider's pathogen resistance, as evidenced by increased cumulative mortality rates and suppressed activities of key immune effectors or ATP levels. The decreased abundance of antibacterial peptides such as lycotoxins and lycosins was also identified. Multi-omics, RT-qPCR, and western blot analyses revealed a set of genes that play roles in the Cd burden response, of which Toll pathway and ribosomal protein genes may be potential contributors to the disturbed immune defense system. These findings expanded the toxicity mechanistic investigation of heavy metals on the fitness parameters of paddy predators.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"298 ","pages":"Article 110307"},"PeriodicalIF":4.3,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144772619","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":"Norethindrone causes oxidative stress, intestinal injury, and disturbed gut microbiota composition in adult female western mosquitofish (Gambusia affinis)","authors":"Junhao Wu ,&nbsp;Meixin Ye ,&nbsp;Congmo Jin ,&nbsp;Jinlin Yang ,&nbsp;Jiefeng Tan ,&nbsp;Ziping Cai ,&nbsp;Xing Hu ,&nbsp;Qianlin Cai ,&nbsp;Yuying Chen ,&nbsp;Yicheng Zhou ,&nbsp;Liping Hou ,&nbsp;Yan-Qiu Liang ,&nbsp;Diyun Chen","doi":"10.1016/j.cbpc.2025.110305","DOIUrl":"10.1016/j.cbpc.2025.110305","url":null,"abstract":"<div><div>Norethindrone (NET), a widely used synthetic progestin, has been consistently detected in diverse aquatic ecosystems, raising significant concerns about its potential ecological risks. In this study, adult female western mosquitofish (<em>Gambusia affinis</em>) were exposed to environmentally relevant concentrations of NET (5.0, 50.0, and 500.0 ng/L) for 42 days to evaluate the toxicity on gastrointestinal (GI) tract. The results demonstrated that NET exposure significantly induced intestinal damage (i.e., increased villus space in the gut, reduced height of columnar epithelial cells, decreased intestinal muscle layer thickness, and diminished goblet cell density). These pathological alterations might ultimately lead to significant growth inhibition in <em>G. affinis</em>. Furthermore, significant alterations in the antioxidant physiology were observed, including elevated levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione S-transferase (GST), and glutathione peroxidase (GPX). Transcriptomic and protein-protein interaction (PPI) analyses demonstrated that NET exposure induced the activation of oxidative stress-associated pathways, particularly the ferroptosis and PI3K/AKT signaling pathways. Finally, 16S rRNA sequencing analysis revealed that NET exposure significantly altered the structure and function of the microbial community within the GI tract. In conclusion, this study clarifies the mechanisms of NET induced oxidative stress and intestinal tissue damage, highlights the health implications of NET exposure in aquatic organisms, and provides critical insights into its ecotoxicological risks.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"298 ","pages":"Article 110305"},"PeriodicalIF":4.3,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788453","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":"Assessment of the ecological risk posed by cypermethrin to surface waters based on a species sensitivity distribution model","authors":"Yingbo Duan ,&nbsp;Yingkun Cao ,&nbsp;Hansen Li ,&nbsp;RuiYang Niu ,&nbsp;Saipei Duan ,&nbsp;Limei Qu ,&nbsp;Weiyan Duan","doi":"10.1016/j.cbpc.2025.110308","DOIUrl":"10.1016/j.cbpc.2025.110308","url":null,"abstract":"<div><div>Cypermethrin, as a type II pyrethroid broad-spectrum insecticide, is often detected in aquatic environments. However, the ecological risk posed by cypermethrin to global surface waters remains uncertain. In this study, the species sensitivity distribution and assessment factor-based methods were used to evaluate the sensitivity of various aquatic organisms to this insecticide, incorporating both acute toxicity and chronic toxicity data. Crustaceans exhibited the highest sensitivity to cypermethrin, whereas algae showed the lowest sensitivity. The acute and chronic hazardous concentrations of cypermethrin affecting 5 % of species (HC₅) in freshwater environments were determined to be 9.2 × 10⁻⁵ and 3.5 × 10⁻⁵ mg/L, respectively. Therefore, it was concluded that cypermethrin is highly toxic to freshwater organisms, in line with previous ecological risk assessments conducted in 12 countries worldwide. Limited data are available on the toxicity of cypermethrin to marine organisms. Existing data suggest a high ecological risk of cypermethrin in the north central coastal zone of Sinaloa, Mexico. Thus, cypermethrin may pose serious ecological risks to aquatic organisms globally and potentially threaten human health.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"298 ","pages":"Article 110308"},"PeriodicalIF":4.3,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144772620","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":"Isolated and combined toxicity of PVC microplastics and copper on Pinctada fucata martensii: Immune, oxidative, and metabolomics insights","authors":"Robert Mkuye ,&nbsp;Xiuyan Yang ,&nbsp;Chuangye Yang ,&nbsp;Edna Bubelwa ,&nbsp;Fortunatus Masanja ,&nbsp;Hagai Nsobi Lauden ,&nbsp;Muhammad Salman ,&nbsp;Yuewen Deng","doi":"10.1016/j.cbpc.2025.110302","DOIUrl":"10.1016/j.cbpc.2025.110302","url":null,"abstract":"<div><div>PVC microplastics (PVC MPs) and copper (Cu) are pervasive marine pollutants with significant ecological impacts. This study analyzed individual and combined effects of PVC microplastics (PVC MPs) at concentrations of 1 and 5 mg/L and copper (Cu) at concentration of 5 μg/L on immune response, oxidative balance, detoxification capacity, and hepatopancreas metabolomics in <em>Pinctada fucata martensii</em>. Pearl oysters were exposed to these stressors for 13 days, followed by a 7 days recovery phase. Immune enzymes: acidic phosphatase (ACP) and alkaline phosphatase (AKP); antioxidant enzymes: catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx); and detoxification enzyme: glutathione S-transferase (GST) were assessed, alongside hepatopancreas metabolomic profiling. Results showed that combined exposure (MPs + Cu) significantly elevated ACP and AKP activities compared to individual treatments, indicating enhanced immune activation. Oxidative stress biomarkers (CAT, SOD, GPx) were significantly higher in co-exposed groups, suggesting synergistic toxicity. Moreover, metabolomic analysis revealed significant alterations in key pathways, including glycerophospholipid metabolism, pentose and glucuronate interconversions, arachidonic acid metabolism, and phosphatidylinositol signaling, reflecting disruptions in membrane integrity, energy metabolism, and inflammatory responses. During recovery, enzyme activities and metabolite trends indicated partial physiological restoration, though co-exposed oysters exhibited prolonged metabolic disturbances. This study highlights the compounded toxicity of MPs and Cu, emphasizing their role in impairing bivalve health through oxidative stress, immune modulation, and metabolic disruption. The findings highlight the need for comprehensive risk assessments of marine pollutant interactions to mitigate ecological and aquacultural impacts.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"298 ","pages":"Article 110302"},"PeriodicalIF":4.3,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752558","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":"Biological effects of planktonic Microcystis and benthic Oscillatoria on macro-benthic animals","authors":"Huiting Yang ,&nbsp;Wei Chen ,&nbsp;Yujia Yao ,&nbsp;Xiaohong Gu ,&nbsp;Huihui Chen ,&nbsp;Qingfei Zeng ,&nbsp;Zhigang Mao ,&nbsp;Tao Xiang","doi":"10.1016/j.cbpc.2025.110301","DOIUrl":"10.1016/j.cbpc.2025.110301","url":null,"abstract":"<div><div>The concurrent presence of cyanobacterial blooms and cyanobacterial derivative pollution in natural freshwater poses serious threats to aquatic biota and human beings. To date, cyanobacteria, especially ignored benthic toxic cyanobacteria, may cause potential harmful impacts on benthic animals. Understanding benthic animals' possible responses to these toxic cyanobacteria is important for assessing cyanobacterial bloom-induced ecological risks. This study investigated the harmful impacts of planktonic <em>Microcystis aeruginosa</em> (generating microcystin) and benthic <em>Oscillatoria</em> sp. (generating cylindrospermopsin) on the feeding behavior, tissue structure, neurotoxicity, oxidative stress, and immunotoxicity of the freshwater macrobenthos clams <em>Lamprotula leai</em> and snails <em>Bellamya aeruginosa</em> under 14-d exposure. Firstly, two cyanobacteria can reduce the clearance rates of clams and snails, causing tissue damage in their digestive glands. Secondly, two cyanobacteria can induce neurotoxicity in clams and snails by altering acetylcholinesterase activities and acetylcholine levels in their digestive glands. Thirdly, two cyanobacteria can lead to oxidative stress in clams and snails by changing the antioxidant enzyme activities, glutathione levels, malondialdehyde levels, and reactive oxygen species levels in their digestive glands. Finally, two cyanobacteria can cause immunotoxicity in clams and snails by altering lysozyme activities in their digestive glands, while two cyanobacteria can also induce inflammatory responses in clams by increasing levels of interleukin-1β and tumor necrosis factor-α in their digestive glands. These data indicated that toxic cyanobacteria can threaten the health of macrobenthos, and the benthic cyanobacteria-induced adverse ecological impacts should not be ignored.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"297 ","pages":"Article 110301"},"PeriodicalIF":4.3,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144724972","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":"6PPD exposure reduced the melanin deposition by inhibiting tyrosinase activity in larval zebrafish","authors":"Chanlin Fang ,&nbsp;Shanshan Di ,&nbsp;Yuekai Zhang ,&nbsp;Xinquan Wang ,&nbsp;Yuanxiang Jin","doi":"10.1016/j.cbpc.2025.110300","DOIUrl":"10.1016/j.cbpc.2025.110300","url":null,"abstract":"<div><div>N-(1,3-Dimethylbutyl)-<em>N</em>′-phenyl-<em>p</em>-phenylenediamine (6PPD), a critical antioxidant in rubber manufacturing, has raised global concerns due to its environmental persistence and toxic transformation products. While its developmental toxicity is increasingly recognized, the mechanisms underlying melanogenesis disruption in fish remain poorly understood. In this study, we systematically investigated 6PPD's effects on melanin synthesis in zebrafish embryos and murine melanoma cells (B16F10). Larval zebrafish were exposed to 10 and 100 μg/L 6PPD exhibited dose-dependent reductions in melanin deposition, suppressed tyrosinase activity and downregulation of melanogenesis-related genes (<em>tyr</em>, <em>mitfa</em>, <em>trp1</em>, <em>trp2</em>, and <em>dct</em>). Notably, the inhibition of tyrosinase activity was closely linked to behavioral impairments, as larvae exposed to 100 μg/L 6PPD showed significantly decreased swimming distance and velocity under light-dark cycles. Molecular docking revealed strong binding affinities between 6PPD and the key melanogenic proteins (Dct, Tyr, Tyrp1a, and Tyrp1b), suggesting direct interference with enzymatic function. Parallel experiments in B16F10 cells confirmed cross-species melanin suppression, with reduced gene expression and melanin synthesis-related protein (Mitfa and Tyr) at subtoxic concentrations (0.5 and 2.5 mg/L), which was also verified by Masson-Fontana staining. These findings demonstrated that 6PPD disrupted conserved melanogenic pathways by targeting enzymatic activity, posing ecological risks to aquatic and terrestrial organisms.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"298 ","pages":"Article 110300"},"PeriodicalIF":4.3,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741377","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}