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Abstract

Protective effects of oleanolic acid on acetaminophen-induced hepatotoxicity in mice.

J Liu, Y Liu, C Madhu and C D Klaassen
Journal of Pharmacology and Experimental Therapeutics September 1993, 266 (3) 1607-1613;
J Liu
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Y Liu
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C Madhu
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C D Klaassen
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Abstract

Oleanolic acid (OA) is a triterpenoid compound that has been shown to protect against a number of hepatotoxicants, and is used in China to treat hepatitis. In the present study, we examined the effect of OA on acetaminophen (AA)-induced acute liver injury in mice and the mechanism(s) of protection. OA pretreatment (25-100 mg/kg s.c. for 3 days) remarkably decreased AA (500 mg/kg i.p.)-induced liver damage in mice, as indicated by decreased serum activities of alanine aminotransferase and sorbitol dehydrogenase, as well as by histopathological observation. Additionally, OA pretreatment mitigated AA (300-450 mg/kg i.v.)-induced depletion in liver glutathione (GSH) content. The protective effect was not evident until 24 hr after a single s.c. injection of OA (300 mg/kg) and lasted for 72 hr. To examine the mechanism of this protection, the biliary and urinary excretion of AA and AA metabolites were measured for 2 hr after AA administration (150 mg/kg i.v.) in bile duct-cannulated mice. OA pretreatment resulted in an increased urinary excretion of AA-glucuronide and a decreased biliary excretion of AA-GSH. Microsomes from OA-pretreated mice, incubated in vitro with AA, produced less benzoquinoneimine intermediate than controls, as determined by the formation of AA-GSH. Hepatic subcellular distribution of [3H] AA to the nuclear fraction was also decreased by OA. OA pretreatment of mice had no influence on liver UDP-glucuronic acid concentration, but increased hepatic glucuronosyltransferase activity toward AA. In summary, OA pretreatment dramatically protects against AA-induced hepatotoxicity in mice.(ABSTRACT TRUNCATED AT 250 WORDS)

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Journal of Pharmacology and Experimental Therapeutics
Vol. 266, Issue 3
1 Sep 1993
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Abstract

Protective effects of oleanolic acid on acetaminophen-induced hepatotoxicity in mice.

J Liu, Y Liu, C Madhu and C D Klaassen
Journal of Pharmacology and Experimental Therapeutics September 1, 1993, 266 (3) 1607-1613;

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Abstract

Protective effects of oleanolic acid on acetaminophen-induced hepatotoxicity in mice.

J Liu, Y Liu, C Madhu and C D Klaassen
Journal of Pharmacology and Experimental Therapeutics September 1, 1993, 266 (3) 1607-1613;
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