Does combined peroxisome proliferator-activated receptors-agonist and pravastatin therapy attenuate the onset of diabetes-induced experimental nephropathy?

Abstract

Objectives: To investigate the combined effects of rosiglitazone and pravastatin on renal functions in early streptozotocin induced diabetic nephropathy (DN).

Methods: This study was carried out at King Khalid University Hospital Animal House, Riyadh, Saudi Arabia from August 2013 to February 2014. Fifty male Wistar rats were assigned to normal control rats and diabetic rats that received saline, rosiglitazone, pravastatin, or rosiglitazone+pravastatin for 2 months. Their weight range was 230-250 gm, and age range was from 18-20 weeks. At the end of experiment, creatinine clearance, and urinary albumin to creatinine ratio (ACR) were measured. Blood samples were analyzed for transferrin, glycosylated hemoglobin (HbA1c), lipid profile, tumor necrosis factor-alpha (TNF-α), intercellular adhesion molecule-1 (ICAM-1), and lipid peroxide.

Results: Rosiglitazone treatment increased creatinine clearance and plasma transferrin, and decreased urinary ACR, HbA1c, plasma TNF-α, ICAM-1, and serum lipid peroxide levels without affecting the altered lipid profile. Pravastatin treatment produced similar results and normalized the lipid alteration. The combination of rosiglitazone and pravastatin was more effective in attenuating the diabetes-induced nephropathy compared with treatment with either drug alone.

Conclusion: The combination strategy of rosiglitazone and pravastatin may provide a potential synergistic renoprotective effect against DN by improving renal functions and reducing indices of DN.

Figure 1

Effect of rosiglitazone and pravastatin on creatinine clearance. All values are represented as mean ± standard deviation. *p=0.000 versus all other groups, ^†p=0.000 versus normal control and rosiglitazone + pravastatin treated diabetic group.

Figure 2

Effect of rosiglitazone and pravastatin on urinary albumin to creatinine ratio (ACR). All values are represented as mean ± standard deviation. *p=0.000 versus all other groups; †p=0.000 versus normal control and rosiglitazone + pravastatin treated diabetic group. ‡p=0.000 versus normal control.

Figure 3

Effect of rosiglitazone and pravastatin on plasma tumor necrosis factor (TNF)-a 2 months after completion of the experiment. All values are represented as mean ± standard deviation. *p=0.000 versus all other groups; †p=0.000 versus normal control and rosiglitazone + pravastatin treated diabetic group.

Figure 4

Effect of rosiglitazone and pravastatin on plasma intercellular adhesion molecule (ICAM-1) 2 months after completion of the experiment. All values are represented as mean ± standard deviation. *p=0.000 versus all other groups; †p=0.024 versus rosiglitazone + pravastatin treated diabetic group.

Figure 5

Effect of rosiglitazone and pravastatin on serum lipid peroxide 2 months after completion of the experiment. All values are represented as mean ± standard deviation. *p=0.000 versus all other groups, †p=0.000 versus normal control and rosiglitazone + pravastatin treated diabetic group.