Effects of Flutriafol Fungicide on the Lipid Accumulation in Human Liver Cells and Rat Liver

Flutriafol (FTF) is a triazole fungicide that can cause liver toxicity through the ingestion of its residues in food and water. However, little is known about the liver toxicity of FTF, particularly nonalcoholic fatty liver disease (NAFLD) in humans. Therefore, the purpose of this study was to investigate whether FTF induces NAFLD in human liver cells and animal liver. HepG2 cells and Sprague Dawley (SD) rats were treated with FTF at doses of 0–640 µM for 24 h and 0–150 mg/kg bw/day for 28 days, respectively. FTF (80, 160, and 320 µM) treatment to cells induced lipid accumulation. FTF (80 and 160 µM)-treated cells had higher levels of cytochrome P450 enzymes and reactive oxygen species and increased mitochondrial membrane potential loss than the control. FTF also increased the mRNA levels of antioxidant enzymes through oxidative stress and nuclear factor erythroid 2-related factor 2 pathways in HepG2 cells. However, a higher level of FTF (320 µM) induced apoptosis. The treatment of SD rats with FTF (2.5–150 mg/kg bw/day) induced fatty infiltration in the liver by impairing liver metabolism and inducing apoptosis. Therefore, our data suggest that human exposure to FTF residues may be a risk factor for liver diseases, such as NAFLD.