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 enzymes in vivo as well as its effects against CCl4-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 CCl4. 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 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 acid (p < 0.01 for 500 microM) resulted in a reduction of glutamate-oxalate-transaminase, lactate dehydrogenase activities and in a good survival rate for the CCl4-intoxicated hepatocytes. Ursolic acid also ameliorated lipid peroxidation in primary cultured rat hepatocytes exposed to CCl4, as demonstrated by a reduction in malondialdehyde production. Moreover, ursolic acid (50-500 microM) 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 CCl4 by maintaining the levels of glutathione and by inhibiting the production of malondialdehyde due to its radical scavenging properties.
Martin-Aragón
S
S
Dpto Farmacología, Facultad de Farmacia Universidad Complutense de Madrid, Spain.
de las Heras
B
B
Sanchez-Reus
M I
MI
Benedi
J
J
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002251:Carbon Tetrachloride / Q000633:toxicity; D002374:Catalase / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D017665:Hydroxyl Radical / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D011897:Random Allocation; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*; D000097245:Ursolic Acid
D000410:Alanine Transaminase; D000975:Antioxidants; D001219:Aspartate Aminotransferases; D002251:Carbon Tetrachloride; D002374:Catalase; D005978:Glutathione; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D017665:Hydroxyl Radical; D013482:Superoxide Dismutase; D014315:Triterpenes; D000097245:Ursolic Acid