Mechanism of Antihepatotoxic Activity of Atractylon, I: Effect on Free Radical Generation and Lipid Peroxidation¹

Abstract

The mechanism of antihepatotoxic action of atractylon, a main sesquiterpenic constituent of Atractylodes rhizomes, was studied. Atractylon inhibited carbon tetrachloride (CCl₄)-induced cytotoxicity in primary cultured rat hepatocytes and CCl₄-induced lipid peroxidation by rat liver microsomes. However, atractylon increased the free radical generation by CCl₄ with rat liver microsomes in the presence of a radical trapping agent, phenyl t-butyl nitrone (PBN). In addition, atractylon generated free radical per se. Experiments using ¹³CCl₄ instead of CCl₄ indicated that the increased free radicals consisted of those from ¹³CCl₄ and from atractylon. Accumulated data support that although both CCl₄ and atractylon generate free radicals respectively by rat liver microsomes, free radical from CCl₄ conducts lipid peroxidation and produces liver lesion, while atractylon forms free radical which scavenges CCl₃ radical in the absence of PBN, inhibits lipid peroxidation by CCl₄ and suppresses CCl₄-induced liver lesion.