The Renal Protective Effects of Cilostazol on Suppressing Pathogenic Thrombospondin-1 and Transforming Growth Factor-β Expression in Streptozotocin-Induced Diabetic Rats

Abstract

Diabetic nephropathy is a major complication facing patients with diabetes mellitus. The renal protective effects of the phosphodiesterase III inhibitor, cilostazol, were investigated in rats with streptozotocin-induced diabetes. Expression of thrombospondin-1 (TSP-1) and transforming growth factor-β (TGF-β) in the kidney was measured by immunohistochemistry and real-time reverse transcription-quantitative polymerase chain reaction analysis in diabetic rats, cilostazol-treated diabetic rats and control rats. Ultrastructural changes in the kidney were also analysed using microscopy. Four weeks after the induction of diabetes, TSP-1 and TGF-β expression was significantly increased in the kidneys of diabetic rats compared with the control and was significantly lower in cilostazol-treated diabetic rats than in the untreated diabetic rats. Microscopy revealed characteristic renal pathology in the diabetic group, which was rarely seen in the cilostazol-treated diabetic rats. In conclusion, this study indicates that cilostazol treatment of diabetic rats effectively prevents pathological kidney changes, possibly via the down-regulation of TSP-1 and TGF-β expression compared with untreated rats.