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Abstract
The protective effects of oleanolic acid on carbon tetrachloride-induced hepatotoxicities
and the possible mechanisms involved in this protection were investigated in mice.
Pretreatment with oleanolic acid prior to the administration of carbon tetrachloride
significantly prevented the increase in serum alanine aminotransferase and lactate
dehydrogenase activity and liver lipid peroxidation in a dose-dependent manner. Hepatic
glutathione levels and glutathione-S-transferase activities were not affected by treatment
with oleanolic acid alone but pretreatment with oleanolic acid protects carbon tetrachloride-induced
depletion of hepatic glutathione levels. The effects of oleanolic acid on the cytochrome
P450 (P450) 2E1, the major isozyme involved in carbon tetrachloride bioactivation
were investigated. Treatment of mice with oleanolic acid resulted in a significant
decrease of P450 2E1-dependent p-nitrophenol and aniline hydroxylation in a dose-dependent
manner. Consistent with these observations, the P450 2E1 expressions were also decreased,
as determined by immunoblot analysis. These results show that the protective effects
of oleanolic acid against the carbon tetrachloride-induced hepatotoxicity may, at
least in part, be due to its ability to block bioactivation of carbon tetrachloride
mainly by the inhibition of expression and activities of P450 2E1.