Comparative Study between the Effect of Pentoxifylline versus Diltiazem versus Rosuvastatin on the Development and Progression of Nephropathy in Streptozotocin Induced Diabetic Rats

Abstract

Background. Diabetic nephropathy is the major cause of end stage renal disease especially in developing countries. Reducing proteinuria is the mainstay of therapy in order to delay the progression of chronic kidney disease. Current therapeutic regimens provide only partial renoprotection, and a substantial number of patients who have proteinuria progress to end stage renal disease. Aim. The aim of this study was to evaluate the effects of pentoxifylline and diltiazem versus rosuvastatin on development and progression of nephropathy in streptozotocin induced diabetic rats and possible mechanisms of action. Materials and Methods. Eighty adult albino rats were randomly divided into eight groups: the first and second groups are normal control and diabetic control. Streptozotocin-induced type 1 diabetes mellitus (DM) model was set up in adult male albino rats by single intraperitoneal injection of streptozotocin (65mg/kg, I.P). The third, the fifth, and the seventh groups are non-diabetic groups of rats receiving pentoxifylline (40mg/kg/day, orally), diltiazem (10 mg/kg/day, i.p.), or rosuvastatin (10mg/kg/day, orally), respectively, for eight weeks. The fourth, the sixth, and the eighth groups are diabetic rats receiving pentoxifylline (40 mg/kg per day, orally), diltiazem (10mg/kg per day, i.p.), or rosuvastatin (10mg/kg/day, orally), respectively, for eight weeks. The glomerular filtration rate, serum urea, creatinine, urine albumin, urine volume changes, Na+ excretion level, K+ excretion level, renal blood flow, renal histopathology, and measurement of antioxidant enzymes activity (GSH, superoxide dismutase) of the different groups were tested compared to control group. Results. At the end of the eight weeks, use of pentoxifylline and rosuvastatin induced significant reduction of serum creatinine, urea, and urine albumin. Also, glomerular filtration rate, renal blood flow, and antioxidant enzymes were significantly improved. There were no significant differences between the two drugs, while diltiazem induced insignificant improvement in the previous parameters. Conclusion. The use of pentoxifylline and rosuvastatin is associated with a reduced risk of diabetic nephropathy by improving oxidative stress. Furthermore, diltiazem insignificantly ameliorates diabetic nephropathy.