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

Authors

Department of Physiology and Biophysics, School of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran

Abstract

Background: Chronic uncontrolled hyperglycemia is the common reason of renal failure.
 

Objectives: 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).
 

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-αagonist) is able to prevent DN progression and improve kidney performance during chronic uncontrolled hyperglycemia possibly through increase in NO bioavailability of kidney.

Keywords


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