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.
Highlights
Diabetic nephropathy is a serious insult of prolonged uncontrolled hyperglycemia
Diabetic rats treated with cilostazol showed significant (p
Glucose dysregulation is associated with accelerated non-enzymatic glycation of proteins and lipids with advanced glycation end products (AGEs) formation which play a pivotal role in pathogenesis of diabetic nephropathy (Singh et al 2014)
Summary
Diabetic nephropathy is a serious insult of prolonged uncontrolled hyperglycemia. It represents the principle reason for end stage renal failure worldwide. Large percentage of diabetic patients develops structural and functional renal alterations which require dialysis or transplantation (Mestry et al 2017). Involvement of AGEs in the development of diabetic angiopathy is strongly evident (Fracasso et al 2019). AGEs/RAGE interaction recruits downstream cascades as oxidative stress, autophagy, pro-inflammatory transcription factors as nuclear factor–κB (NF-κB), cytokines (interleukins and tumor necrosis factor-α), Intercellular Adhesion Molecule-1 (ICAM-1) and Vascular Cell Adhesion Molecule-1 (VCAM-1) with subsequent vascular remodeling and long lasting vascular injury which trigger atherosclerosis and endothelial damage in diabetic microvascular insult (Xu et al 2016). RAGE activation contributes to vasoconstriction via enhancing endothelin-1 expression and interfering with nitric oxide biosynthesis (Quade-Lyssy et al 2013)
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