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 (CCl 4 )-induced cytotoxicity in primary cultured rat hepatocytes and CCl 4 -induced lipid peroxidation by rat liver microsomes. However, atractylon increased the free radical generation by CCl 4 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 13 CCl 4 instead of CCl 4 indicated that the increased free radicals consisted of those from 13 CCl 4 and from atractylon. Accumulated data support that although both CCl 4 and atractylon generate free radicals respectively by rat liver microsomes, free radical from CCl 4 conducts lipid peroxidation and produces liver lesion, while atractylon forms free radical which scavenges CCl 3 radical in the absence of PBN, inhibits lipid peroxidation by CCl 4 and suppresses CCl 4 -induced liver lesion.