Mitochondrial mechanism of florfenicol-induced nonalcoholic fatty liver disease in zebrafish using multi-omics technology

文献类型: 外文期刊

第一作者: Zhang, Lin

作者: Zhang, Lin;Du, Yang;Li, Yameng;Wang, Tiancai;Pan, Yecan;Mu, Xiyan;Qiu, Jing;Qian, Yongzhong;Zhang, Lin;Xue, Xiaofeng

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关键词: Florfenicol; Zebrafish; Non-alcoholic fatty liver disease; Mitochondrial dysfunction; Multi-omics analysis

期刊名称:JOURNAL OF HAZARDOUS MATERIALS ( 影响因子:11.3; 五年影响因子:12.4 )

ISSN: 0304-3894

年卷期: 2025 年 486 卷

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收录情况: SCI

摘要: Florfenicol (FF), a third-generation chloramphenicol antibiotic widely used in food-producing animals, has become a "pseudopersistent" environmental contaminant, raising concerns about its potential ecological and human health impacts. However, its bioaccumulation behavior and hepatotoxic mechanisms remain poorly understood. This study aims to address these gaps with a 28-day exposure experiment in adult zebrafish at 0.05 and 0.5 mg/L FF. Multiomic analyses (metabolomics, lipidomics, and transcriptomics), combined with histological and mitochondrial function assessments, were employed. Higher bioaccumulation was observed at 0.05 mg/L, potentially due to metabolic saturation at higher concentrations. Histological analysis revealed significant hepatic steatosis (>5 % steatosis area), indicative of moderate nonalcoholic fatty liver disease (NAFLD). Multiomic data demonstrated global dysregulation in energy metabolism, including marked alterations in lipids (accumulation of toxic sphingolipids, excessive fatty acids, and acylglycerol), amino acids, tricarboxylic acid cycle intermediates, and nucleotides. Crucially, mitochondrial dysfunction was identified as a central mechanism, with impaired respiratory chain activities, adenosine triphosphate depletion, elevated reactive oxygen species, and oxidative stress promoting NAFLD progression. These findings highlight mitochondrial impairment and oxidative stress as key drivers of FF-induced hepatotoxicity, providing novel insights into its toxicological mechanisms and emphasizing the ecological risks posed by antibiotic pollution in aquatic systems.

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