Renal ischemia reperfusion (I/R) causes distant organ damage such as cardiac injury and diabetes mellitus type 2 (T2DM) increases sensitivity to I/R and cardiac injury. Hence, the present study examined whether treatment with exenatide improve the cardiac injury in a renal I/R injury using a T2DM rat model. To fulfill the objective, male wistar rats were divided into five groups. In vivo renal I/R were performed in both T2DM and normal rats. Each protocol comprised ischemia for 30 min followed by reperfusion 24 hrs and exenatide treatment period 14 days before induction of ischemia. Diabetic rats that underwent renal I/R in exhibited significant increase in the serum concentrations of lactate dehydrogenase (p < 0.01) and creatinine kinase (p < 0.01) as compared to non-diabetic rats. Lipid peroxidation, xanthine oxidase activity, myeloperoxidase activity and nitric oxide level in cardiac tissue were significantly (p < 0.05) increased after I/R in diabetic rats compared to non-diabetic rats. Antioxidant enzymes like glutathione (p < 0.05) and catalase (p < 0.05) were significantly reduced after I/R in diabetic rats compared to non-diabetic rats. Exenatide treatment significantly (p < 0.05) normalized these biochemical parameters compared to diabetic I/R rats. In conclusion, exenatide treatment attenuated cardiac injury induced by renal I/R in diabetic rats. This is the first study in which exenatide was used to prevent cardiac injury induced by I/R in diabetes via NO generation and neutrophil sequestration in the cardiac tissue.
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