Resveratrol-mediated cardioprotection against myocardial ischemia-reperfusion injury was revoked by statin-induced mitochondrial alterations

Abstract

Resveratrol is well known for its antioxidant potential and ability to preserve mitochondrial function, reported attenuating ischemia-reperfusion (IR) injury in the heart. The present study investigates resveratrol on IR injury in rat hearts treated with statin for 14 days. Male Wistar rats were used in this study, and statin-induced cardiac metabolic alterations were monitored after the administration of simvastatin (80 mg/kg). IR was instigated by the Langendroff perfusion system and measured the physiological and biochemical changes. The basal level changes in ECG, ANP, and BNP expression and CoenzymeQ10 level were altered in statin-treated animals compared to the normal rat heart. The animals treated with statin demonstrated higher IR injury (measured via low rate pressure product (88.4%), increased histological alterations, prominent mitochondrial dysfunction (NQR: IR-72%, Stat IR-67%; SQR: IR-71%, Stat IR-74%; COX: IR-58%, Stat IR-52%) than the normal rat heart underwent similar protocols. Administration of heart with resveratrol recovered the IR associated hemodynamic indices in normal heart subjected to IR but failed to impart a similar effect in the statin-treated heart. Our results demonstrated that resveratrol failed to reverse the IR-associated cardiac injury and functional abnormalities in statin-treated rat hearts subjected to IR but effective in IR challenged normal heart.