Residues of glyphosate (GLY) are widely detected in aquatic systems, raising potential environmental threats and public health concerns, but the mechanism underlying GLY-induced hepatotoxicity in fish has not been fully elucidated yet. This study was designed to explore the hepatotoxic mechanism using juvenile common carp exposed to GLY for 45 d, and plasma and liver samples were collected at 15 d, 30 d, and 45 d to analyze the assays. First, GLY-induced hepatic damage was confirmed by serum liver damage biomarker and hepatic histopathological analysis. Next, changes in oxidative stress biomarkers, gene expression levels of pro- and anti-inflammatory cytokines, and lipid metabolism-related parameters in collected samples were analyzed to clarify their roles in GLY-induced hepatic damage. Data showed that oxidative stress was an early event during GLY exposure, followed by hepatic inflammatory response. Lipid metabolism disorder was a late event during GLY exposure, as evidenced by overproduced hepatic free fatty acids, enhanced lipogenesis-related gene expression levels, reduced lipolysis-related gene expression levels, and resultant hepatic lipid accumulation. Collectively, these findings demonstrate that GLY induces hepatotoxicity in fish through involvement of oxidative stress, inflammatory response, and lipid metabolism disorder, which are intimately interrelated with each other during GLY exposure.

草甘膦 (GLY) 残留在水生系统中广泛检测到，引发了潜在的环境威胁和公共卫生问题，但 GLY 引起鱼类肝毒性的机制尚未完全阐明。本研究旨在探讨GLY幼鱼的肝毒性机制，并在15天、30天和45天收集血浆和肝脏样本进行分析。首先，通过血清肝损伤生物标志物和肝组织病理学分析证实了GLY诱导的肝损伤。接下来，分析收集样本中氧化应激生物标志物、促炎和抗炎细胞因子的基因表达水平以及脂质代谢相关参数的变化，以阐明它们在 GLY 诱导的肝损伤中的作用。数据显示，氧化应激是 GLY 暴露期间的早期事件，随后是肝脏炎症反应。脂质代谢紊乱是 GLY 暴露期间的晚期事件，表现为肝脏游离脂肪酸过量产生、脂肪生成相关基因表达水平增强、脂肪分解相关基因表达水平降低以及由此导致的肝脏脂质积累。总的来说，这些研究结果表明，GLY 通过参与氧化应激、炎症反应和脂质代谢紊乱而诱导鱼类肝毒性，这些在 GLY 暴露期间彼此密切相关。