College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, 310014, China.
Environ Toxicol. 2018 Jun;33(6):650-658. doi: 10.1002/tox.22550. Epub 2018 Feb 16.
Imazalil (IMZ), which is a widely used fungicide, can accumulate in the body and threaten an animal's health. However, this fungicide has adverse effects on aquatic organisms and ultimately affects human health when it leaches into the environment. Our research tried to determine that if IMZ might cause liver damage and its potential to cause-related diseases. In this study, male adult C57BL/6 mice were exposed to 0.1, 0.5, or 2.5 mg/kg body weight IMZ in drinking water for 15 weeks. Then, we evaluated the liver damage at the physiological, biochemical, and transcriptome levels in mice after chronic IMZ exposure. We observed serious ballooning degeneration of hepatocytes in the IMZ-treated groups. And IMZ induced oxidative stress and caused the disorders of bile acid metabolism in mice. In addition, the transcriptome data showed that IMZ has substantial influence on several pathways, including metabolic pathways for drug metabolism, RNA transport, and bile secretion. We further confirmed that the mRNA expression of the key genes involved in oxidative stress and bile acid metabolism were changed of mice exposed to IMZ. Our data suggested that chronic IMZ exposure could induce hepatotoxicity in mice at the physiological, biochemical, and transcriptome levels.
抑霉唑（IMZ）是一种广泛使用的杀菌剂，可能在体内蓄积，威胁动物健康。然而，这种杀菌剂对水生生物有不良影响，当其渗入环境时，最终会影响人类健康。我们的研究试图确定 IMZ 是否可能导致肝脏损伤以及其导致相关疾病的潜力。在这项研究中，雄性成年 C57BL/6 小鼠通过饮用水暴露于 0.1、0.5 或 2.5mg/kg 体重的 IMZ 中，持续 15 周。然后，我们评估了慢性 IMZ 暴露后小鼠在生理、生化和转录组水平上的肝损伤。我们观察到 IMZ 处理组的肝细胞出现严重的气球样变性。IMZ 诱导氧化应激，并导致小鼠胆汁酸代谢紊乱。此外，转录组数据表明，IMZ 对包括药物代谢、RNA 转运和胆汁分泌在内的几个途径有实质性影响。我们进一步证实，暴露于 IMZ 的小鼠中与氧化应激和胆汁酸代谢相关的关键基因的 mRNA 表达发生了变化。我们的数据表明，慢性 IMZ 暴露可在生理、生化和转录组水平诱导小鼠肝毒性。
