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


CONCLUSIONS
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.
Physiology Department, College of Medicine, King Saud University, PO 2925 (29), Riyadh 11461, Kingdom of Saudi Arabia. Tel. +966 (11) 8052154 / 8050193. Fax. +966 (11) 8054684. E-mail. hayam_gad@hotmail.com.
Hayam I
HI
Gad
D000818:Animals; D003404:Creatinine / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D006442:Glycated Hemoglobin / Q000187:drug effects / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists; D017035:Pravastatin / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use; D014168:Transferrin / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
D003404:Creatinine; D006442:Glycated Hemoglobin; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007004:Hypoglycemic Agents; D018799:Intercellular Adhesion Molecule-1; D008054:Lipid Peroxides; D047492:Peroxisome Proliferator-Activated Receptors; D017035:Pravastatin; D000077154:Rosiglitazone; D045162:Thiazolidinediones; D014168:Transferrin; D014409:Tumor Necrosis Factor-alpha