Cardiac Damage Induced by Renal Ischemia/Reperfusion Injury in Hyperlipidemic Rats: Role of PPAR-α Agonist

Abstract

In view of the reported efficacy of peroxisome proliferator-activated receptor-α in renal ischemia/reperfusion (I/R) injury, the present study was designed to investigate the effect of fenofibrate on cardiac damage induced by renal I/R in hyperlipidemic rats. Male Wistar rats were divided into five groups: Group 1, normal control; Group 2, hyperlipidemic control; Group 3, renal I/R injury; Group 4, hyperlipidemic + renal I/R injury; and Group 5, hyperlipidemic +renal I/R injury + fenofibrate. Hyperlipidemia was induced by feeding the rats with cholesterol (500 mg/kg per oral) in hydrogenated ground nut oil (as a vehicle) for 4 weeks. At the end of the fourth week, renal I/R injury was induced by occlusion of both renal vascular pedicles for 60 minutes, followed by 24-hour reperfusion. In the treatment group, fenofibrate (100 mg/kg per oral, dissolved in water containing 0.2% methyl cellulose) was given 2 weeks before I/R injury. At the end of the experiment, blood and heart were isolated for biochemical analysis. Hyperlipidemic I/R rats have significantly higher levels of cardiac lipid peroxidation, xanthine oxidase, nitric oxide and myeloperoxidase, and lower levels of antioxidant enzymes (reduced glutathione, superoxide dismutase and catalase) compared to non-hyperlipidemic I/R rats, the levels of which were restored after treatment with fenofibrate. Cardiac functional enzymes were normalized after the administration of fenofibrate. This study elucidated the oxidative role of cardiac damage induced by renal I/R via inflammatory mediators, which was attenuated by fenofibrate.