Schisandrin B protects against myocardial ischemia-reperfusion injury by enhancing myocardial glutathione antioxidant status

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 exam ined 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 perfusa te produced protective effect, as evidenced by the significant decrease in the extent of lactate dehydrogenase leakage as well as an improvement in co ntractile force recovery. Myocardial protection afforded by N-acetyl-L-cyst eine supplemented perfusate was not accompanied by the enhancement in contr actile 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 enhance ment in myocardial glutathione antioxidant status, as indicated by signific ant reductions in both the extent of IR-induced reduced glutathione depleti on and inhibition of Se-glutathione peroxidase and glutathione reductase ac tivities. In contrast, the inability of DDB pretreatment to enhance myocard ial glutathione antioxidant status resulted in a failure in preventing IR i njury. The ensemble of results suggests that the myocardial protection affo rded by Sch B pretreatment, which was unlikely due to free radical scavengi ng action, may be mainly mediated by the enhancement of myocardial glutathi one antioxidant status, particularly under oxidative stress conditions.