Chronic exposure of mice to low doses of imazalil induces hepatotoxicity at the physiological, biochemical, and transcriptomic levels.

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.