Effect of adding rosuvastatin to enalapril on prevention of streptozotocin-induced diabetic nephropathy in rats

Abstract EN

Background : Diabetic nephropathy (DN) is the major cause of chronic renal failure.

Several mechanisms could be involved : advanced glycation end products (AGEs), activation of protein kinase C (PKC), oxidative stress and over-expression of transforming growth factor-β1 (TGF-β1).

Aim : evaluation of the effect of adding rosuvastatin to enalapril on the development of diabetic nephropathy.

Methods : seventy rats were used: normal control and 6 diabetic groups ; diabetic control group, enalapril group; received enalapril 5 mg / Kg / d, rosuvastatin 1 and 5 mg groups ; two groups received rosuvastatin 1or 5 mg / kg / d respectively, enalapril + Rosuvastatin groups ; two groups received enalapril + rosuvastatin 1 mg / kg / d or enalapril + rosuvastatin 5 mg / kg / d.

At start and every 4 weeks ; body weight ; blood glucose and kidney function tests were assessed.

At the end ; kidney / body weight ratio, lipid profile, serum total nitrite / nitrate, reduced glutathione and TGF-β1 were assessed.

Results : Hyperglycemia was associated with loss in body weight, lipid profile abnormalities, impaired kidney function, increased serum TGF-β1 and total nitrite / nitrate and decreased reduced glutathione.

Enalapril improved all measures except hyperglycemia and lipid profile.

Rosuvastatin (1.5 mg / kg / d) ameliorated all the measures ; the higher dose was more effective than the lower dose.

The concomitant administration of enalapril and rosuvastatin 1 mg / kg was the best therapy to produce renal protection.

Conclusions : Addition of rosuvastatin to enalapril ameliorated features of diabetic nephropathy largely than enalapril alone.

The current study encourage adding a low dose of rosuvastatin to potentiate the effect of enalapril to prevent development of diabetic nephropathy.