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

{"title":"Neurotoxicity induced by difenoconazole in zebrafish larvae via activating oxidative stress and the protective role of resveratrol","authors":"Chunlan Liu ,&nbsp;Jiansheng Zhu ,&nbsp;Renfei Zhu ,&nbsp;Yifei Yin","doi":"10.1016/j.cbpc.2025.110208","DOIUrl":"10.1016/j.cbpc.2025.110208","url":null,"abstract":"<div><div>Difenoconazole (DIF) is a typical triazole fungicide detected in the aquatic ecosystem and organisms. However, the neurotoxic effects of DIF remain largely unknown. This study aimed to investigate the neurotoxicity of DIF in zebrafish and the underlying neuroprotective properties of resveratrol (RES, an antioxidant polyphenol). Zebrafish embryos/larvae were treated with 0.6 and 1.2 mg/L DIF from 4 to 96 h post fertilization (hpf) and neurodevelopment was systematically assessed. DIF induced developmental toxicity and aberrant neurobehaviors, including decreased movement time, swimming distance and clockwise rotation times. DIF suppressed the neurogenesis of the central nervous system (CNS) in <em>HuC:egfp</em> transgenic zebrafish and the length of motor neuron axon in <em>hb9:egfp</em> transgenic zebrafish. DIF inhibited cholinesterase activities and downregulated neurodevelopment related genes. DIF also increased oxidative stress via excessive production of reactive oxygen species and decreased activities of antioxidant enzymes, subsequently triggering neuronal apoptosis in the brain. RES partially reinstated DIF-induced neurotoxicity and developmental toxicity by inhibiting excessive oxidative stress and apoptosis, suggesting the involvement of oxidative stress in DIF-induced neurotoxicity. Overall, this study identified the potential mechanisms underlying DIF-induced neurotoxicity and suggested RES as a promising therapeutic strategy.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"295 ","pages":"Article 110208"},"PeriodicalIF":3.9,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860280","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":"Assessing neonicotinoid pollution in aquatic ecosystems: A systematic review and bibliometric-content analysis","authors":"Qinglin Yang ,&nbsp;Xiaoqi Tang ,&nbsp;Yuzhuo He ,&nbsp;Xianyun Wu ,&nbsp;Xiaobo Yu ,&nbsp;Yanhong Li ,&nbsp;Zhengli Wu","doi":"10.1016/j.cbpc.2025.110207","DOIUrl":"10.1016/j.cbpc.2025.110207","url":null,"abstract":"<div><div>The widespread use and distribution of neonicotinoids (NNIs) have led to their significant accumulation in aquatic ecosystems, posing serious ecological risks to non-target species and the human food chain. This review employed bibliometric analysis to examine global research from 2013 to 2023, highlighting key trends, advancements, and research priorities. Moreover, we summarized the global distribution of NNIs in various aquatic environments through content analysis and assessed their ecotoxicological effects under controlled laboratory conditions. Our findings indicate a growing global concern about NNIs in aquatic systems, with research efforts primarily concentrated in regions most affected by their use. The presence of NNIs across different water bodies highlights widespread contamination, with China facing particularly severe pollution. However, research on the safety of NNIs in aquatic environments remains insufficient. Future studies should focus on monitoring chronic NNIs exposure and its long-term ecological impacts through field research. Moreover, developing microbial formulations, integrating phytoremediation, and combining multiple technologies for synergy are crucial for developing sustainable strategies to mitigate NNIs pollution, protect human health, and preserve aquatic ecosystems.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"294 ","pages":"Article 110207"},"PeriodicalIF":3.9,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848336","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":"Dinotefuran exposure induces immunotoxicity in zebrafish embryos","authors":"Yunshuo Chen ,&nbsp;Yacan Gong ,&nbsp;Dan Li ,&nbsp;Weiwei Feng ,&nbsp;Yao Chen ,&nbsp;Ting Zhao ,&nbsp;Liuqing Yang ,&nbsp;Guanghua Mao ,&nbsp;Xiangyang Wu","doi":"10.1016/j.cbpc.2025.110206","DOIUrl":"10.1016/j.cbpc.2025.110206","url":null,"abstract":"<div><div>As a typical neonicotinoid insecticide, dinotefuran (DIN) has immunotoxicity, but its immunotoxicity effects on aquatic organisms and its molecular mechanisms are not known. In this study, zebrafish embryos were used as model to reveal its immunotoxicity and its mechanism from the perspective of inflammatory response. Zebrafish larvae were exposed to DIN at environmentally relevant concentrations (0, 2, 200, and 2000 mg/L) for 120 h, followed by comprehensive analyses of immune cell populations, immune marker activities, oxidative stress levels, and gene expression profiles. The results showed that the number of neutrophils and macrophages, two types of innate immune cells, was significantly reduced, and the activities of the immune markers, lysozyme (LYS), immunoglobulin M (IgM), and complement protein C3, were significantly inhibited. The level of oxidative stress in zebrafish larvae was significantly elevated and antioxidant enzyme activities were markedly inhibited in a dose-dependent manner after exposure to DIN. In this case, pro-inflammatory cytokines such as TNF-α, IL-6 and IL-1β were also abnormally expressed, and the expression levels of the genes related to the NF-κB pathway and the JNK-STAT pathway, <em>tlr4a, myd88, nf-κb p65, jak1, jak2</em>, and <em>stat3</em>, were elevated. The expression levels of genes related to the antioxidant signaling pathway Nrf2-keap1 signaling pathway were suppressed. Taken together, our results suggest that DIN exposure causes damage to the immune system of zebrafish embryos-larvae, generating oxidative stress and inflammatory responses that lead to immunotoxicity.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"295 ","pages":"Article 110206"},"PeriodicalIF":3.9,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855945","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":"Oxidative and metabolic responses in Crassostrea gasar under combined stressors of elevated temperature and microplastic exposure","authors":"Júlia Ferreiro ,&nbsp;Maidana da Silva Idiarte ,&nbsp;Júlia Oliveira ,&nbsp;Suamy Cruz ,&nbsp;Gabriela Soares Correa ,&nbsp;Larissa Müller ,&nbsp;Juliane Ventura-Lima","doi":"10.1016/j.cbpc.2025.110204","DOIUrl":"10.1016/j.cbpc.2025.110204","url":null,"abstract":"<div><div>This study investigates two critical threats to species such as the oyster <em>Crassostrea gasar</em>: elevated temperatures and microplastic (MP) contamination. To assess the combined effects of MP and temperature, oysters were exposed to different temperatures (20 °C, 26 °C, and 28 °C, with 20 °C considered the control group) and to a nominal concentration of 100 μg/L of MP (spherical polystyrene, 1.1 μm) at the same temperatures for 7 days. Oxidative stress parameters were analyzed, including the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST), as well as glutathione (GSH) levels and lipid peroxidation. Additionally, energy metabolism indicators, such as glucose and lactate levels and lactate dehydrogenase activity, were evaluated, along with the accumulation of MP in the gills and digestive glands of oysters. The results showed that regardless of temperature both gills and digestive gland accumulated MP. Besides, the thermal stress increased GST activity in both tissues and altered GSH levels. At the highest temperature, MP exposure led to increased SOD activity in the gills and decreased CAT activity in the digestive gland. GST activity was elevated in oysters exposed to MP at 20 °C, alongside higher GSH levels. At 26 °C, glucose and lactate levels, as well as lactate dehydrogenase activity, were significantly elevated. Co-exposure to MP notably affected oysters at 26 °C, reducing glucose levels in the gills while increasing them in the digestive gland. The Integrated Biomarker Response (IBR) index revealed that co-exposure had a more pronounced impact on the gills than on the digestive gland. Overall, this study underscores how a commercially important oyster species could be adversely affected by the combined impacts of global warming and MP contamination.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"294 ","pages":"Article 110204"},"PeriodicalIF":3.9,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844484","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 crosstalk between autophagy and apoptosis mechanism of hemocytes in Chlamys farreri under B[a]P exposure in vitro","authors":"Ning Zhang,&nbsp;Luqing Pan,&nbsp;Qilong Liao,&nbsp;Fengjun Lei,&nbsp;Ruixue Tong,&nbsp;Yaobing Li","doi":"10.1016/j.cbpc.2025.110202","DOIUrl":"10.1016/j.cbpc.2025.110202","url":null,"abstract":"<div><div>The impact of polycyclic aromatic hydrocarbons (PAHs) on the immune function of marine animals has garnered significant attention. <em>C. farrei</em> is frequently exposed to pollutants and has only innate immunity. To delve more deeply into the immunotoxicity mechanism of PAHs in <em>C. farrei</em>, its hemocytes were cultured <em>in vitro</em> as they were the primary drivers of immune activities. The autophagy and apoptosis of hemocytes are essential components of the immune response. The exposure of pollutant, autophagy and apoptosis of immune cells are often disrupted, leading to immunodeficiency. In aquatic animals, the mechanism of autophagy and apoptosis in hemocytes remains unclear, and the crosstalk between the two needs to be further investigated. To evaluate the mechanism of autophagy and apoptosis of hemocytes <em>in vitro</em>, 0 μM, 1 μM, 2.5 μM or 5 μM Benzopyrene (B[<em>a</em>]p) was chosen. Experimental results demonstrated that B[<em>a</em>]P triggered autophagosome formation, but also caused significant damage to lysosomes, resulting in a compromised autophagic flux. B[<em>a</em>]P causes an increase in apoptosis levels in hemocytes of <em>C. farreri</em> by affecting the transcriptional level of AIF. To further explore the crosstalk mechanism between the two, activator and inhibitor of autophagy were used. After adding autophagy activator or inhibitor, the present results indicated that Lysosomal function determined the patency of autophagic flux. When massive autophagosomes accumulate, it leads to a much higher rate of apoptosis through caspase-dependent apoptotic pathway. Lysosomal damage further leads to apoptosis and inhibit autophagy. In the B[<em>a</em>]P-treated group, immunological parameters were markedly decreased due to autophagy and apoptosis of hemocytes. The immunotoxicity mechanism of B[<em>a</em>]P in <em>C. farreri</em> hemocytes was investigated in present study, which enriched the immunotoxicity network.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"294 ","pages":"Article 110202"},"PeriodicalIF":3.9,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143823958","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":"Involvement of the weak metabolic function in cardiovascular toxicity induced by idebenone in zebrafish","authors":"Jiashuo Zhou ,&nbsp;Yanan Yang ,&nbsp;Jingcheng Zhao,&nbsp;Te Zheng,&nbsp;Yun Zhang","doi":"10.1016/j.cbpc.2025.110203","DOIUrl":"10.1016/j.cbpc.2025.110203","url":null,"abstract":"<div><div>Idebenone (IDE) is a commonly used psychotropic drug in the clinic. However, the cardiovascular toxicity of IDE has not been reported previously. Therefore, we evaluated the safety of IDE and preliminarily elucidated the mechanism of cardiovascular toxicity induced by IDE using zebrafish as the model organism. In this study, wild-type AB zebrafish, and transgenic zebrafish <em>Tg(cmcl2:EGFP)</em> with green fluorescence-labelled cardiomyocytes were used as the research objects. We evaluated the effects of IDE on the sinus venosus-bulbus arteriosus (SV-BA) distance, ejection fraction, ventricular short-axis shortening rate, blood flow rate, and the staining area and intensity of cardiac erythrocytes. The toxic mechanism of IDE was elucidated using transcriptomics and Quantitative real-time PCR (qRT-PCR). We found that high concentrations of IDE could cause acute poisoning of some zebrafish within a short period (6 h), mainly characterized by severe cardiac venous stasis. IDE decreased the blood flow and reduced the red blood cell stained area in the heart region of some zebrafish. The results of transcriptome analysis and qRT-PCR showed that the expression of genes related to drug metabolism and lipid metabolism was significantly down-regulated in zebrafish with IDE-induced cardiovascular toxicity. We believe that IDE may be more likely to cause acute cardiovascular toxicity in organisms with weak metabolic enzyme function. The present study investigated the mechanism of the toxic effects of IDE using a zebrafish model and laid the foundation for a more comprehensive understanding of the cardiovascular toxicity of IDE.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"294 ","pages":"Article 110203"},"PeriodicalIF":3.9,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143823959","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":"Impact of environmental salinity on the MAPK-NFAT5 pathway in Trachemys scripta elegans and its role in osmoregulaton","authors":"Xin Niu ,&nbsp;Yingnan Lu ,&nbsp;Yue Yuan,&nbsp;Jiao Li,&nbsp;Yunjuan Xiao,&nbsp;Haitao Shi,&nbsp;Meiling Hong,&nbsp;Li Ding","doi":"10.1016/j.cbpc.2025.110201","DOIUrl":"10.1016/j.cbpc.2025.110201","url":null,"abstract":"<div><div>Globally, sea level rise (SLR) leads to salinization of coastal freshwater, in where organisms might be affected and in turn promote osmoregulation and adaptation in response to freshwater salinization. <em>Trachemys scripta elegans</em> a freshwater turtle species, exhibits remarkable tolerance to varying salinity environments, yet the underlying regulatory mechanisms remain poorly understood. This study aimed to elucidate the molecular mechanisms of osmoregulation in this species based on previous RNA-seq data. Our findings revealed that when exposed to 5 PSU (5 ‰) and 15 PSU (15 ‰) salinities, the turtles exhibited increased concentrations of ions (Na⁺, K⁺) and urea in urine, along with elevated osmotic pressures in both plasma and urine. Additionally, the protein levels of aquaporins (AQPs) and transporters of ions and organic osmolytes in the kidney were upregulated in saline water. Notably, the transcriptional level of the hypertonic regulator NFAT5 was significantly elevated, accompanied by an increase in phosphorylated NFAT5 levels in the nucleus of renal tubular epithelial cells. Furthermore, we observed upregulated phosphorylated levels of MAPKs in saline water. The use of MAPK inhibitors effectively blocked the transcription of NFAT5 and osmoregulatory target genes. Collectively, these results suggest that <em>T. scripta elegans</em> activates the MAPK-NFAT5 signaling pathway to modulate osmotic pressure in adaptation to saline water environments. Our study provides valuable insights into the osmoregulatory responses of aquatic organisms to saline environments and aids in understanding the adaptability of organisms inhabiting coastal areas facing rising sea levels.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"294 ","pages":"Article 110201"},"PeriodicalIF":3.9,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771545","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 exposure to antimony elicits endocrine disturbances, leading to PCOS and ovarian fibrosis in female zebrafish","authors":"Zhongqian Cen ,&nbsp;Shenghan Lv ,&nbsp;Qing Li ,&nbsp;Jingyun Zhang ,&nbsp;ShiXue Mei ,&nbsp;Xia Hu ,&nbsp;Aijiang Yang","doi":"10.1016/j.cbpc.2025.110198","DOIUrl":"10.1016/j.cbpc.2025.110198","url":null,"abstract":"<div><div>Antimony (Sb) is an estrogenic metal. Exogenous exposure to Sb can affect estrogen levels and their receptor expression in organisms, exerting estrogen-disrupting effects and even inducing polycystic ovary syndrome (PCOS), which is accompanied by the progression of ovarian fibrosis. To investigate the pathological mechanism of this reproductive damage caused by Sb exposure, we exposed female zebrafish to Sb solution for 18 days for acute toxicity experiments. The results showed that Sb exposure affected the changes of GnRH, FSH, LH, E2 and T levels on the HPG axis, which disrupted the balance of sex steroid hormones in the internal environment of zebrafish and progression of PCOS. Furthermore, Sirius red staining revealed significant fibrosis in the ovarian tissues of Sb-exposed female zebrafish. This study adopted transcriptome sequencing and Western Blotting to explore the mechanisms of action. The biological processes and signaling pathways potentially associated with Sb-induced ovarian fibrosis were predicted by using GO annotation and KEGG pathway enrichment analysis, such as ECM receptors, TGF-β/Smad and WNT/β-catenin. The experiment results showed that Sb induced up-regulation of the transcription levels of the pro-fibrotic factors <em>tgf-β3</em>, <em>wnt10a</em>, <em>ctnnb1</em>, and β-catenin protein expression, suggesting the activation of the WNT/β-catenin pathways and TGF-β/Smad. Sb exposure led to up-regulation of ECM-related genes <em>col2a1a</em>, <em>itgb1b.2</em>, <em>lamc1</em>, <em>fn1a</em> and up-regulation of fibrosis markers α-SMA, Fn1a, col4a2 protein expression, Therefore, we hypothesized that Sb exposure activates the TGF-β/Smad and WNT/β-catenin pathways, leading to abnormal ECM deposition and promoting the progression of ovarian fibrosis in zebrafish.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"294 ","pages":"Article 110198"},"PeriodicalIF":3.9,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771533","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":"Chronic exposure to bisphenol S is associated with antagonistic neurobehavioral transformation and cleaved caspase 3 induced neurodegeneration in zebrafish brain","authors":"Bhabani Sankar Sahoo ,&nbsp;Lilesh Kumar Pradhan ,&nbsp;Prerana Sarangi ,&nbsp;Jayashree Digal ,&nbsp;Suvam Bhoi ,&nbsp;Pradyumna Kumar Sahoo ,&nbsp;Sai Aparna ,&nbsp;Sangeeta Raut ,&nbsp;Saroj Kumar Das","doi":"10.1016/j.cbpc.2025.110200","DOIUrl":"10.1016/j.cbpc.2025.110200","url":null,"abstract":"<div><div>Bisphenol S (BPS), a widely used bisphenol analogue, has been increasingly detected in aquatic environments, raising concerns about its potential neurotoxic effects. However, the mechanism underlying the neurotoxicity induced by BPS remains elusive. In this context, our present study was aimed to investigate the impact of temporal BPS exposure towards precocious development of neurobehavioral transformation and neurodegeneration in zebrafish brain. Heightened monoamine oxidase (MAO) activity is associated with induction of aggressive behavioural response. In line with earlier report, our findings following mirror biting test advocated that temporal BPS exposure is associated with gradual genesis of aggressive neurobehavioral response and is correlated with augmented MAO activity and downregulation of tyrosine hydroxylase (TH) expression in zebrafish brain. Our further observation towards native neurobehavioral response as regulated by periventricular grey zone (PGZ) of optic tectum (TeO) of brain showed that duration dependent exposure to BPS is associated with gross transformation in scototaxis and explorative behaviour of zebrafish. Concurrently, our objective was also predestined to emphasize the detrimental effect of BPS on brain biochemistry and neuromorphology. In this line, our findings showed that BPS-persuaded heightened oxidative stress is linked with augmented chromatin condensation and apoptotic cell death as depicted through cleaved caspase-3 expression in zebrafish brain. To understand neuromorphological integrity of PGZ region through expression of NeuN, our findings advocated a significant downregulation following temporal exposure to BPS. In a nutshell, the gross observation delineates the strong neurodegenerative potential of BPS coupled through neurobehavioral transformation, oxidative stress and neuromorphological alteration in zebrafish brain.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"294 ","pages":"Article 110200"},"PeriodicalIF":3.9,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771537","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":"New insights into the cytotoxic mechanism of marine-fungus-derived citrinin in three-dimensional Hepa1-6 cell model","authors":"Keyue Wu ,&nbsp;Qingyue Meng ,&nbsp;Xuhua Nong ,&nbsp;Xinye Chen ,&nbsp;Yonghong Liu ,&nbsp;Simon Wing-Fai Mok ,&nbsp;Riming Huang ,&nbsp;Xiaoyong Zhang","doi":"10.1016/j.cbpc.2025.110196","DOIUrl":"10.1016/j.cbpc.2025.110196","url":null,"abstract":"<div><div>Although recent studies have demonstrated that Marine-fungus-derived citrinin (MFDC) has a significant cytotoxic effect in traditional two-dimensional (2D) monolayer cell culture and animal models, its precise cytotoxic mechanism, particularly in a three-dimensional (3D) cell culture model remains unclear. In this study, a 3D Hepa1-6 cell model based on Matrigel was used to investigate the potential cytotoxic mechanism of MFDC (0–100 μg/mL). The results revealed that, after treatment of 60–100 μg/mL MFDC, the increases of reactive oxygen species (ROS), lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in 2D cell model were more significant than those in 3D cell model. In addition, the metabolomic results revealed that the significantly altered metabolic pathways were pyrimidine metabolism and vitamin B6 metabolism, which might be related to the interference of MFDC in the pyrimidine synthesis pathway, as well as the upregulation of pyridoxine 5'phosphate oxidase and pyridoxal kinase activities. This study was the first to compare the cytotoxicology of 2D and Matrigel-based 3D cell models after MFDC induction, and to detect differences in cell metabolites after MFDC induction in 3D cell models, providing a new scientific basis for the use of a 3D cell model and a novel research idea for the cellular damage caused by MFDC.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"294 ","pages":"Article 110196"},"PeriodicalIF":3.9,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143746559","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}