CILOSTAZOL ATTENUATES DIABETIC NEPHROPATHY IN RATS VIA ELEVATION OF PLASMA SOLUBLE RECEPTOR FOR ADVANCED GLYCATION END-PRODUCTS

Document Type : Original Article

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Department of clinical pharmacology, Faculty of Medicine, Zagazig University

Abstract

Cilostazol is a phosphodiesterase III inhibitor with antiplatelet and vasodilating properties. Cilostazol effectively attenuated severity of diabetic angiopathy. However, the underlying mechanisms involved in its beneficial effect against diabetic nephropathy are not fully elucidated. Type-1 diabetic rats received cilostazol (25mg/kg/day, oral for 12 weeks). Fasting blood glucose, serum lipids, renal nuclear factor κB (NF-κB) and interluckin-6 (IL-6), kidney function markers, oxidative stress parameters were examined. The plasma soluble receptor for advanced glycation end products (sRAGE) was assayed. Renal advanced glycation end products (AGEs) level was assayed. Renal histopathological study was also performed. The results showed improvement in kidney structure and function post cilostazol treatment. Furthermore, cilostazol elevated the circulating plasma sRAGE level and decreased renal AGEs, NF-κ B and IL-6 levels.  Moreover, the renal levels of reduced glutathion, superoxide dismutase and heme oxygenase-1 increased associated with reduction in malondialdehyde suggesting enriched antioxidant status in the kidney.   Conclusion, Cilostazol ameliorates diabetic renal injury which may be, in part, due to elevation of circulating plasma sRAGE, lowering of renal AGEs level and in other part the anti-inflammatory action and enhancement of the renal antioxidant status.

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