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

Chronic uncontrolled hyperglycemia is the common reason of renal failure. We aimed to assess the possible protective effects of PPAR-α agonist (fenofibrate) on kidney performance and nitric oxide (NO) level of kidney in experimental model of diabetic nephropathy (DN). 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. 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. Our findings indicate that fenofibrate (PPAR-α agonist) is able to prevent DN progression and improve kidney performance during chronic uncontrolled hyperglycemia possibly through increase in NO bioavailability of kidney.