Oleanolic acid protects against myocardial ischemia-reperfusion injury by enhancing mitochondrial antioxidant mechanism mediated by glutathione and alpha-tocopherol in rats.
The effect of oleanolic acid (OA) pretreatment on myocardial ischemia-reperfusion (I-R) injury was investigated using an ex vivo rat heart model. Pretreatment with OA at daily doses (0.6 and 1.2 mmol/kg) for 3 days significantly protected against I-R injury in isolated rat hearts, as evidenced by the decrease in the extent of lactate dehydrogenase (LDH) leakage and improvement in contractile force recovery. The cardioprotection was associated with a slight increase in mitochondrial reduced glutathione (GSH) level and a significant increase in mitochondrial alpha-tocopherol (alpha-TOC) level, when compared with the unpretreated I-R group. To further investigate the mechanism of myocardial protection, pretreatment with a single dose of OA (1.2 mmol/kg) produced a time-dependent protection against myocardial I-R injury as assessed by LDH leakage, with the maximum extent of protection occurring at 48 hour post-dosing. The maximum cardioprotection was associated with parallel increases in mitochondrial GSH and alpha-TOC levels in ischemic-reperfused hearts, with the stimulation of the alpha-TOC level being optimal. Furthermore, buthionine sulfoximine/phorone (BSO/PHO) treatment, while abolishing the enhancing effect of OA on mitochondrial GSH, did not completely abrogate the cardioprotection against I-R injury. The remnant cardioprotection was associated with an increase in mitochondrial alpha-TOC level, when compared with the unpretreated I-R group with BSO/PHO. The results suggest that the cardioprotection afforded by OA pretreatment against I-R injury may at least in part be attributed to the enhancement of mitochondrial antioxidant mechanism mediated by GSH and alpha-TOC, particularly under I-R conditions. Abbreviations. BSO:buthionine sulfoximine GSH:reduced glutathione I-R:ischemia-reperfusion alpha-LA:alpha-lipoic acid LDH:lactate dehydrogenase OA:oleanolic acid PHO:phorone alpha-TOC:alpha-tocopherol.
Du
Ying
Y
Department of Biochemistry, Hong Kong University of Science & Technology, Clear Water Bay, China.
Ko
Kam Ming
KM
D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005978:Glutathione / Q000378:metabolism; D008929:Mitochondria, Heart / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D009828:Oleanolic Acid / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018384:Oxidative Stress; D008517:Phytotherapy; D010946:Plants, Medicinal; D051381:Rats; D017207:Rats, Sprague-Dawley; D024502:alpha-Tocopherol / Q000378:metabolism
D000975:Antioxidants; D002316:Cardiotonic Agents; D009828:Oleanolic Acid; D005978:Glutathione; D024502:alpha-Tocopherol