Soy isoflavones reduce acetaminophen-induced liver injury by inhibiting cytochrome P-450-mediated bioactivation and glutathione depletion and increasing urinary drug excretion in rats

Soy isoflavones (SI) are phytochemicals with various biological activities. Acetaminophen can cause acute liver injury when overdosed. In this study, to investigate the effects of SI on the metabolism and toxicity of acetaminophen in liver, rats were fed a controlled diet with or without 120 mg/kg SI-rich product for 2 weeks and were then intraperitoneally injected with acetaminophen. Cytochrome P-450 (CYP), phase II enzymes, membrane transporters, and glutathione in liver were evaluated. Acetaminophen-induced elevations in plasma alanine aminotransferase activity and decreases in liver glutathione levels were ameliorated in rats treated with SI. SI reduced hepatic CYP2E1 and CYP3A activities and acetaminophen-protein adduct contents. Hepatic UDP-glucuronosyltransferase activity and urinary acetaminophen excretion were increased by SI after acetaminophen treatment. Protein expression of multidrug-resistance-associated protein 2/3 and connexin 32 in liver, however, was not changed by SI. Our results indicate that SI-rich product may act as functional food which can reduce acetaminophen-induced hepatotoxicity.