Zhang Lin, Du Yang, Li Yameng, Wang Tiancai, Pan Yecan, Xue Xiaofeng, Mu Xiyan, Qiu Jing, Qian Yongzhong
Key Laboratory of Agri-food Quality and Safety of Ministry of Agriculture and Rural Affairs, Institute of Quality Standards and Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, Beijing 100081, China; Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Beijing 100093, China.
Key Laboratory of Agri-food Quality and Safety of Ministry of Agriculture and Rural Affairs, Institute of Quality Standards and Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, Beijing 100081, China.
J Hazard Mater. 2025 Mar 15;486:136958. doi: 10.1016/j.jhazmat.2024.136958. Epub 2024 Dec 25.
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.
氟苯尼考（FF）是一种广泛应用于食用动物的第三代氯霉素类抗生素，已成为一种“假持久性”环境污染物，引发了人们对其潜在生态和人类健康影响的担忧。然而，其生物累积行为和肝毒性机制仍知之甚少。本研究旨在通过在成年斑马鱼中进行为期28天、浓度为0.05和0.5毫克/升的氟苯尼考暴露实验来填补这些空白。采用了多组学分析（代谢组学、脂质组学和转录组学），并结合组织学和线粒体功能评估。在0.05毫克/升时观察到更高的生物累积，这可能是由于较高浓度下的代谢饱和所致。组织学分析显示肝脏有明显的脂肪变性（脂肪变性面积>5%），表明存在中度非酒精性脂肪性肝病（NAFLD）。多组学数据表明能量代谢存在整体失调，包括脂质（有毒鞘脂、过量脂肪酸和酰基甘油的积累）、氨基酸、三羧酸循环中间体和核苷酸的显著变化。至关重要的是，线粒体功能障碍被确定为核心机制，呼吸链活性受损、三磷酸腺苷耗竭、活性氧升高以及氧化应激促进了NAFLD的进展。这些发现突出了线粒体损伤和氧化应激是氟苯尼考诱导肝毒性的关键驱动因素，为其毒理学机制提供了新的见解，并强调了水生系统中抗生素污染所带来的生态风险。
