Protective Effect of Resveratrol against Ischemia-Reperfusion Injury via Enhanced High Energy Compounds and eNOS-SIRT1 Expression in Type 2 Diabetic Female Rat Heart.

Natacha Fourny,Monique Bernard,Martine Desrois,Carole Lan,Eric Sérée

doi:10.3390/nu11010105

Abstract

Type 2 diabetic women have a high risk of mortality via myocardial infarction even with anti-diabetic treatments. Resveratrol (RSV) is a natural polyphenol, well-known for its antioxidant property, which has also shown interesting positive effects on mitochondrial function. Therefore, we aim to investigate the potential protective effect of 1 mg/kg/day of RSV on high energy compounds, during myocardial ischemia-reperfusion in type 2 diabetic female Goto-Kakizaki (GK) rats. For this purpose, we used 31P magnetic resonance spectroscopy in isolated perfused heart experiments, with a simultaneous measurement of myocardial function and coronary flow. RSV enhanced adenosine triphosphate (ATP) and phosphocreatine (PCr) contents in type 2 diabetic hearts during reperfusion, in combination with better functional recovery. Complementary biochemical analyses showed that RSV increased creatine, total adenine nucleotide heart contents and citrate synthase activity, which could be involved in better mitochondrial functioning. Moreover, improved coronary flow during reperfusion by RSV was associated with increased eNOS, SIRT1, and P-Akt protein expression in GK rat hearts. In conclusion, RSV induced cardioprotection against ischemia-reperfusion injury in type 2 diabetic female rats via increased high energy compound contents and expression of protein involved in NO pathway. Thus, RSV presents high potential to protect the heart of type 2 diabetic women from myocardial infarction.

Highlights

Cardiovascular (CV) complications are the first causes of morbidity and mortality in type 2 diabetic patients, in women [1]
It is known that the risk of myocardial infarction is five times higher in type 2 diabetic women compared with non-diabetic women, while this risk is only multiplied by two in men [3,4]
Plasma glucose was significantly increased in GK, GK-P, and GK-RSV in comparison to control group (CTRL) (p < 0.0001)

Summary

Introduction

Cardiovascular (CV) complications are the first causes of morbidity and mortality in type 2 diabetic patients, in women [1]. Cardio-protection is widely recognized in women, and surprisingly, is suppressed with type 2 diabetes, with more serious CV consequences in women than in men [2]. It is known that the risk of myocardial infarction is five times higher in type 2 diabetic women compared with non-diabetic women, while this risk is only multiplied by two in men [3,4]. Mortality due to myocardial infarction is higher in women than in men in type 2 diabetes [5]. Endothelial damage is one likely hypothesis for CV complications in type 2 diabetes. Desrois et al reported a higher endothelial damage in female GK rat hearts

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