Augmentation of Aflatoxin B1 Hepatotoxicity by Endotoxin: Involvement of Endothelium and the Coagulation System

Aflatoxin B1 (AFB1) is a fungal toxin that causes both acute hepatotoxicity and liver carcinoma in exposed humans and ani-mals. Previous studies have shown that exposure of rats to non-toxic doses of bacterial lipopolysaccharide (LPS) augments AFB1 acute hepatotoxicity, resulting in enhanced injury to hepatic pa-renchymal cells and bile ducts. At larger doses, LPS causes dam-age to sinusoidal endothelial cells (SECs) and activation of the coagulation system. Accordingly, we tested the hypothesis that treatment of rats with AFB1 and LPS damages SECs and activates the coagulation system, which is critical for potentiation of AFB1 hepatotoxicity by LPS. Male, Sprague-Dawley rats were given 1 mg/kg AFB1 (ip), then 4 hours later 7.4 10 6 EU/kg LPS was administered (iv). A time-dependent injury to SECs and paren-chymal cells was observed in AFB1/LPS-cotreated animals tha