AMELIORATION OF MYOCARDIAL INJURY IN DIABETIC RATS BY KAEMPFEROL

Abstract

Objective: Ischemic heart disease is one of the leading causes of global mortality. Reperfusion i.e. restoration of the blood to the ischemic heart is a necessary therapeutic approach to maintain cardiac function. However, reperfusion elicits a series of adverse events that paradoxically cause injury of myocardium. Kaempferol (KMP), a naturally occurring polyphenolic compound which is present in tea, broccoli, propolis and grapefruit and possesses anti-oxidant, anti-inflammatory, anti-apoptotic, anti-cancer, neuroprotective, cardioprotective and anti-diabetic properties. Therefore, Present study, aimed to investigate the effect of kaempferol in ischemia-reperfusion (IR) model of myocardial injury in rats. Design and method: Male albino wistar rats were used for this study. They were divided into sham, IR-control, KMP-20+IR and KMP 20 per se groups. KMP was administered daily to the rats at a dose of 20 mg/kg intraperitoneally for a 15 day period. The dose of KMP was determined by our earlier studies in isoproterenol-induced myocardial infarction in rats. On the 15th day, ischemia was developed by one-stage ligation of left anterior descending coronary artery for 45 minutes followed by reperfusion for 60 minutes. Hemodynamic parameters (systolic and diastolic blood pressures mean arterial pressure, heart rate, left ventricular end diastolic pressure, maximal positive and negative rate of left ventricular pressure) were recorded. Rats were then sacrificed, the heart was excised and processed for biochemical (determination of the levels of MDA, GSH, SOD, catalase, Ck-MB, LDH), morphological (H&E staining and electron microscopy) and molecular studies (western blot analysis, immunohistochemistry and TUNEL assay). Results: KMP pretreatment significantly alleviated IR injury by maintaining cardiac function, attenuating oxidative stress and preserving cardiac morphology. Also, there was a decrease in the level of inflammatory markers (TNF-alpha, IL-6 and NF-kappa-B), inhibition of expression of active JNK and p38 proteins and activation of ERK1/2, a pro-survival kinase. Further, apoptosis was markedly reduced as was evident from decreased expression of pro-apoptotic proteins (Bax and Caspase-3), TUNEL positive cells and increased levels of anti-apoptotic proteins (Bcl-2). Conclusions: KMP safeguards against IR injury by attenuating inflammation and apoptosis through modulation of MAPK pathway and rectification of redox state of the myocardium.