Hepatic Lipid Peroxidation and Intracellular Calcium Accumulation in Ethanol Potentiated Aflatoxin B₁ Toxicity

Abstract

The possible role of hepatic lipid peroxidation and Ca²⁺ in enhanced hepatotoxicity of aflatoxin B₁ (AFB₁) by ethanol was examined along with changes in hepatic glutathione in male rats. Hepatic glutathione (GSH) was markedly decreased (43.9%) at 12 h after AFB₁ administration in rats treated with ethanol (4.0 g/kg BW) and AFB₁ (2.0 mg/kg BW) when compared to AFB₁ alone. At 24 h after AFB₁ administration, hepatic lipid peroxide levels in subcellular fractions, particularly in microsomes, were significantly increased (76.9%) in rats treated with ethanol and AFB₁ following the decrease in hepatic GSH content. Hepatic lipid peroxide levels returned to normal values at about 48 h after AFB₁ administration. Furthermore, Ca²⁺ in whole liver (60.9%), microsomes (83.8%) and mitochondria (51.2%) were significantly increased in the rats treated with ethanol and AFB₁ as compared to those rats treated with AFB₁ alone at 48 h after toxin administration. The increase in hepatic Ca²⁺ in rats treated with ethanol and AFB₁ was a possible consequence of the increase in hepatic lipid peroxide. These findings suggest that there is a close relationship between hepatic GSH content, lipid peroxidation and intracellular accumulation of Ca²⁺. The pronounced effects on hepatic lipid peroxidation and intracellular accumulation of Ca²⁺ could play a role in ethanol-induced potentiation of AFB₁ hepatotoxicity in rats.