Pharmacological modification of endogenous antioxidant enzymes by ursolic acid on tetrachloride-induced liver damage in rats and primary cultures of rat hepatocytes

The purpose of this study was to investigate possible protective effects of ursolic acid against CCl4-induced alterations of antioxidant defence enzym es in vivo as well as its effects against CCl4-intoxication in vitro. Pre-t reatment of rats with ursolic acid significantly reduced serum levels of gl utamate-oxalate-transaminase and glutamate-pyruvate-transaminase previously increased by administration of CCl4. Treatment with ursolic acid also sign ificantly reversed the decreased superoxide dismutase, catalase, glutathion e reductase, glutathione peroxidase activities and glutathione levels in th e liver, as the concentration of reduced glutathione was increased and the content of oxidized glutathione decreased in ursolic acid treated groups. L evels of lipid peroxidation were higher in the CCl4 group but the increase was also reduced after drug treatment (p < 0.01 for 1, 2.5 and 5 mmol/kg). In vitro results indicated that addition to the culture medium of ursolic a cid (p < 0.01 for 500 muM) resulted in a reduction of glutamate-oxalate-tra nsaminase, lactate dehydrogenase activities and in a good survival rate for the CCl4-intoxicated hepatocytes. Ursolic acid also ameliorated lipid pero xidation in primary cultured rat hepatocytes exposed to CCl4, as demonstrat ed by a reduction in malondialdehyde production. Moreover, ursolic acid (50 -500 muM) showed radical scavenging properties in terms of hydroxyl formati on. The results obtained suggest that ursolic acid treatment can normalize the disturbed antioxidant status of rats intoxicated with CCl4 by maintaining t he levels of glutathione and by inhibiting the production of malondialdehyd e due to its radical scavenging properties.