In Vitro and In Vivo Study on the Toxic Effects of Propiconazole Fungicide in the Pathogenesis of Liver Fibrosis.

ABSTRACT

Propiconazole (PCZ) is a hepatotoxic triazole fungicide. There are insufficient data on how PCZ induces liver fibrosis in humans. This study aimed to investigate the effect of PCZ on liver fibrosis and its underlying mechanisms. HepG2 cells and Sprague-Dawley rats were exposed to PCZ at doses of 0-160 µM (3-72 h) and 0.5-50 mg/kg body weight/day (28 days), respectively. PCZ-treated cells activated intracellular oxidative stress via cytochrome P450 and had higher mRNA levels of interleukin-1ß, tumor necrosis factor-α, matrix metalloproteinase (MMP)-2, MMP-9, and transforming growth factor-ß (TGF-ß) than the control. PCZ treatment in cells induced a morphological transition with E-cadherin decrease and vimentin and Snail increase via the oxidative stress and TGF-ß/Smad pathways. PCZ administration in rats induced liver fibrosis through pathological changes, epithelial-mesenchymal transition, and collagen deposition. Thus, our data suggest that exposure of PCZ to humans may be a risk factor for the functional integrity of the liver.