The effects of Schisandrin B (Sch B) and dimethyl-4, 4'-dimethoxy-5,6,5',6'dimethylene-dioxy-biphenyl-2,2'-bicarboxylate (DDB) treatment on myocardial ischemia-reperfusion (IR) injury in isolated perfused rat hearts were examined under both in vitro and ex vivo conditions. In vitro administration of liposome-entrapped Sch B or DDB during reperfusion did not protect against myocardial IR injury, whereas ascorbic acid or Trolox supplemented perfusate produced protective effect, as evidenced by the significant decrease in the extent of lactate dehydrogenase leakage as well as an improvement in contractile force recovery. Myocardial protection afforded by N-acetyl-L-cysteine supplemented perfusate was not accompanied by the enhancement in contractile force recovery. In ex vivo experiment, pretreatment of Sch B (0.6/1.2 mmol/kg/day x 3) protected against IR-induced myocardial damage in a dose-dependent manner. The myocardial protection was associated with an enhancement in myocardial glutathione antioxidant status, as indicated by significant reductions in both the extent of IR-induced reduced glutathione depletion and inhibition of Se-glutathione peroxidase and glutathione reductase activities. In contrast, the inability of DDB pretreatment to enhance myocardial glutathione antioxidant status resulted in a failure in preventing IR injury. The ensemble of results suggests that the myocardial protection afforded by Sch B pretreatment, which was unlikely due to free radical scavenging action, may be mainly mediated by the enhancement of myocardial glutathione antioxidant status, particularly under oxidative stress conditions.
