Hepatoprotection of oleanolic acid is related to its inhibition on mitochondrial permeability transition.
The protective effects of oleanolic acid (OA) on carbon tetrachloride (CCl4)-induced liver mitochondrial damage and the possible mechanisms were investigated. Pretreatment with OA prior to the administration of CCl4 significantly suppressed the increases of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (4.2- and 19.9-fold, respectively) in a dose-dependent manner in mice. The dissipation of mitochondrial membrane potential (14.8%) and intra-mitochondrial Ca2+ overload (2.1-fold) in livers of CCl4-insulted mice were also dose-dependently prevented by pretreatment with 20, 50 or 100 mg/kg OA. In addition, the effects of OA on liver mitochondria permeability transition (MPT) induced by Ca2+ were assessed by measuring the change in mitochondrial membrane potential, release of matrix Ca2+ and mitochondrial swelling in vitro. The results showed that preincubation with 50 or 100 microg/ml OA obviously inhibited the Ca2+-induced mitochondrial swelling, mitochondrial membrane depolarization and intra-mitochondrial Ca2+ release. It could be concluded that OA has protective effects on liver mitochondria and the mechanisms underlying its protection may be related to its inhibitory action on MPT.
Tang
Xin-Hui
XH
State Key Laboratory of Pharmaceutical Biotechnology and School of Medicine, Nanjing University, Nanjing, P. R. China.
Gao
Jing
J
Fang
Feng
F
Chen
Jin
J
Xu
Li-Zhi
LZ
Zhao
Xiao-Ning
XN
Xu
Qiang
Q
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002118:Calcium / Q000493:pharmacokinetics; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism*; D008933:Mitochondrial Swelling / Q000187:drug effects*; D009828:Oleanolic Acid / Q000494:pharmacology*
D009828:Oleanolic Acid; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D002118:Calcium