Evaluation of PPAR-α Agonist effect on Kidney Performance Through Increment of Nitric Oxide During Hyperglycemia-Induced Nephropathy in Rat

Abstract

Background: Chronic uncontrolled hyperglycemia is the common reason of renal failure. Objectives: We aimed to assess the possible protective eects of PPAR- agonist (fenofibrate) on kidney performance and nitric oxide (NO) level of kidney in experimental model of diabetic nephropathy (DN). Materials and Methods: Male Wistar rats were randomly divided into four groups (n = 6); Normal, Normal treatment, Diabetic and Diabetic treatment. Rats were made diabetic by an intravenous injection of streptozotocin (40 mg/kg). After 72 hours, blood samples were collected for approving diabetes and the rats with blood glucose above 400 mg/dL were considered as diabetic animals. Treated groups received orally fenofibrate for 8 weeks (80 mg/kg/day). At the end, blood samples were collected for measuring blood glucose and creatinine. Finally, NO content and histopathological assessments of kidney were assessed at termination of experiment. Results: Fenofibrate did not change the blood glucose of normal or diabetic rats. Diabetes increased the proteinuria (82%) and blood creatinine of diabetic rats (4.51 0.45 mg/dL) compared to normal rats (0.66 0.14 mg/dL). Chronic hyperglycemia also decreased the content of renal NO (37%) compared with normal rats in accompany with histopathological damages. Fenofibrate significantly decreased the proteinuria (80%) and blood creatinine of diabetic rats (1.66 0.23 mg/dL). The content of NO increased in the kidney of both treated rats (31%). Fenofibrate also improved the histopathological changes of diabetic kidney. Conclusions: Our findings indicate that fenofibrate (PPAR- agonist) is able to prevent DN progression and improve kidney perfor- mance during chronic uncontrolled hyperglycemia possibly through increase in NO bioavailability of kidney.