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

• Published in: Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie 2001, Vol.53 (2), p.199-206
• Main Authors: Martin-Aragón, S., de las Heras, B., Sanchez-Reus, M.I., Benedi, J.
• Format: Article
• Language: English
• Subjects: antioxidant; CCl 4; hepatocytes; liver; rats; Ursolic acid
• ISSN: 0940-2993; 1618-1433
• DOI: 10.1078/0940-2993-00185

The purpose of this study was to investigate possible protective effects of ursolic acid against CCl 4-induced alterations of antioxidant defence enzymes in vivo as well as its effects against CCl 4-intoxication in vitro. Pre-treatment of rats with ursolic acid significantly reduced serum levels of glutamate-oxalate-transaminase and glutamate-pyruvate-transaminase previously increased by administration of CCl 4. Treatment with ursolic acid also significantly reversed the decreased superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase activities and glutathione levels in the liver, as the concentration of reduced glutathione was increased and the content of oxidized glutathione decreased in ursolic acid treated groups. Levels of lipid peroxidation were higher in the CCl 4 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 acid (p < 0.01 for 500 μM) resulted in a reduction of glutamate-oxalate-transaminase, lactate dehydrogenase activities and in a good survival rate for the CCl 4-intoxicated hepatocytes. Ursolic acid also ameliorated lipid peroxidation in primary cultured rat hepatocytes exposed to CCl 4, as demonstrated by a reduction in malondialdehyde production. Moreover, ursolic acid (50—500 μM) showed radical scavenging properties in terms of hydroxyl formation. The results obtained suggest that ursolic acid treatment can normalize the disturbed antioxidant status of rats intoxicated with CCl 4 by maintaining the levels of glutathione and by inhibiting the production of malondialdehyde due to its radical scavenging properties.