The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Cilostazol ameliorates diabetic nephropathy by inhibiting high-glucose-induced apoptosis

  • Chian, Chien-Wen (Division of Nephrology, Department of Paediatrics, Changhua Christian Hospital) ;
  • Lee, Yung-Shu (Department of Urology, Taipei City Hospital) ;
  • Lee, Yi-Ju (Department of Pathology, Chung Shan Medical University Hospital) ;
  • Chen, Ya-Hui (Department of Medical Research, Changhua Christian Hospital) ;
  • Wang, Chi-Ping (Department of Clinical Biochemistry, Chung Shan Medical University Hospital) ;
  • Lee, Wen-Chin (Division of Nephropathy, Department of Internal Medicine, Chang Bing Show-Chwan Memborial Hospital) ;
  • Lee, Huei-Jane (Department of Clinical Biochemistry, Chung Shan Medical University Hospital)
  • Received : 2020.02.26
  • Accepted : 2020.07.21
  • Published : 2020.09.01
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Abstract

Diabetic nephropathy (DN) is a hyperglycemia-induced progressive development of renal insufficiency. Excessive glucose can increase mitochondrial reactive oxygen species (ROS) and induce cell damage, causing mitochondrial dysfunction. Our previous study indicated that cilostazol (CTZ) can reduce ROS levels and decelerate DN progression in streptozotocin (STZ)-induced type 1 diabetes. This study investigated the potential mechanisms of CTZ in rats with DN and in high glucose-treated mesangial cells. Male Sprague-Dawley rats were fed 5 mg/kg/day of CTZ after developing STZ-induced diabetes mellitus. Electron microscopy revealed that CTZ reduced the thickness of the glomerular basement membrane and improved mitochondrial morphology in mesangial cells of diabetic kidney. CTZ treatment reduced excessive kidney mitochondrial DNA copy numbers induced by hyperglycemia and interacted with the intrinsic pathway for regulating cell apoptosis as an antiapoptotic mechanism. In high-glucose-treated mesangial cells, CTZ reduced ROS production, altered the apoptotic status, and down-regulated transforming growth factor beta (TGF-β) and nuclear factor kappa light chain enhancer of activated B cells (NF-κB). Base on the results of our previous and current studies, CTZ deceleration of hyperglycemia-induced DN is attributable to ROS reduction and thereby maintenance of the mitochondrial function and reduction in TGF-β and NF-κB levels.

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References

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