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

Background: Chronic uncontrolled hyperglycemia is the common reason of renal failure.Objectives: We aimed to assess the possible protective effects of PPAR- agonist (fenofibrate) on kidney performance and nitricoxide (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 andDiabetic treatment. Rats weremadediabetic by an intravenous injection of streptozotocin (40 mg/kg). After 72 hours, blood sampleswere collected for approving diabetes andthe rats with blood glucose above400mg/dL were considered as diabetic animals. Treatedgroups received orally fenofibrate for 8 weeks (80 mg/kg/day). At the end, bloodsamples were collected for measuring blood glucoseand 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%)andbloodcreatinine of diabetic rats (4.51 0.45 mg/dL) compared to normal rats (0.66 0.14 mg/dL). Chronic hyperglycemia also decreasedthe content of renal NO (37%) compared with normal rats in accompany with histopathological damages. Fenofibrate significantlydecreased the proteinuria (80%) and blood creatinine of diabetic rats (1.66 0.23 mg/dL). The content of NOincreased in the kidneyof both treated rats (31%). Fenofibrate also improved the histopathological changes of diabetic kidney.Conclusions: Our findings indicate that fenofibrate (PPAR- agonist) is able to preventDNprogression and improve kidney performanceduring chronic uncontrolled hyperglycemia possibly through increase in NO bioavailability of kidney.

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

Nitric Oxide , Nephropathy , PPAR- Agonist , Fenofibrate , Diabetes Mellitus