Investigation Of Mptp Pore Mediated Mechanism Of Action Of Resveratrol On Myocardial Ischemia-Reperfusion Injury


Thesis Type: Post Graduate

Institution Of The Thesis: Gazi Üniversitesi, Sağlık Bilimleri Enstitüsü, Turkey

Approval Date: 2015

Student: GÜRHAN CEBE

Consultant: FATMA AKAR

Abstract:

Many studies have shown that resveratrol has cardioprotective effect against ischemia- reperfusion injury. Opening of mPTP during ischemia-reperfusion causes mitochondrial swelling, ATP depletion, oxidative phosphorylation and apoptosis/necrosis. The aim of this study is to investigate the effects of atractyloside (ATR), mPTP opener, on cardioprotective effects of resveratrol. For this aim 250-300g Wistar rat anesthetized with ketamine hydrochloride and xylazine then thorax was immediately opened and heart was placed in oxygenized ice-cold Krebs-Heinseleit solution Then heart was mounted on Langendorff apparatus quickly. Hearts were assigned into four groups: In the first group (control), after isolation of the hearts 25 min stabilization with retrograde perfusion was applied. In the second group (resveratrol), after 15 min stabilization period 10 min resveratrol (10 µM) perfusion was applied in order to induce chemical preconditioning. In the third group (atractilocide) after 15 min stabilization period 10 min atractyloside (100 µM) perfusion was applied. In the fourth group (atractyloside + resveratrol), after 5 min stabilization period, heart was perfused with atractyloside (3, 10, 30 and 100 µM) and resveratrol (10 µM) separately for 10 min. For all these groups, 30 min global ischemia was followed by 120 min reperfusion. Infarct size Left Ventricular Development Pressure (LVDP), Left Ventricular End-Diastolic Pressure (LVEDP), ±dP/dtmax, Rate Pressure Product (RPP) were evaluated. Hearts were dyed with TTC at the end of reperfusion in order to evaluate infarct size. Hemodynamic parameters were measured and evaluated by MP35 recording system with water-filled latex balloon. Resveratrol administration significantly improved infarcts area, LVDP, LVEDP, ± dP/dtmax, and RPP values compared to the control group. Co- administration with atractyloside 30 µM and 100 µM significantly eliminate resveratrol- induced effect against ischemia-reperfusion injury on LVEDP, ±dP/dtmax and RPP. These results demostrate that mPTP openers as atractyloside may eliminate the protective effect of resveratrol and vice versa, resveratrol reversed the mPTP opening induced by atractyloside. Resveratrol can be used to prevent mPTP opening induced myocardial ischemia reperfusion injury as a mPTP inhibitor.