Korean J Physiol Pharmacol.  2020 Sep;24(5):403-412. 10.4196/kjpp.2020.24.5.403.

Cilostazol ameliorates diabetic nephropathy by inhibiting highglucose- induced apoptosis

  • 1Division of Nephrology, Department of Paediatrics, Changhua Christian Hospital, Changhua 500, Taiwan
  • 2Department of Urology, Taipei City Hospital, Taipei 10341, Taiwan
  • 3Department of Pathology, Chung Shan Medical University Hospital, Taichung 40221, Taiwan
  • 4Department of Medical Research, Changhua Christian Hospital, Changhua 500, Taiwan
  • 5Department of Clinical Biochemistry, Chung Shan Medical University Hospital, Taichung 40221, Taiwan
  • 6Division of Nephropathy, Department of Internal Medicine, Chang Bing Show-Chwan Memborial Hospital, Changhua 505, Taiwan
  • 7Institute of Biochemistry, Microbiology and Immunology, Medical College, Chung Shan Medical University, Taichung 40221, Taiwan
  • 8Department of Biochemistry, School of Medicine, College of Medicine, Chung Shan Medical University, Taichung 40221, Taiwan


Diabetic nephropathy (DN) is a hyperglycemia-induced progressivedevelopment of renal insufficiency. Excessive glucose can increase mitochondrialreactive oxygen species (ROS) and induce cell damage, causing mitochondrial dysfunction.Our previous study indicated that cilostazol (CTZ) can reduce ROS levelsand decelerate DN progression in streptozotocin (STZ)-induced type 1 diabetes.This study investigated the potential mechanisms of CTZ in rats with DN and in highglucose-treated mesangial cells. Male Sprague–Dawley rats were fed 5 mg/kg/day ofCTZ after developing STZ-induced diabetes mellitus. Electron microscopy revealedthat CTZ reduced the thickness of the glomerular basement membrane and improvedmitochondrial morphology in mesangial cells of diabetic kidney. CTZ treatmentreduced excessive kidney mitochondrial DNA copy numbers induced by hyperglycemiaand interacted with the intrinsic pathway for regulating cell apoptosis as anantiapoptotic mechanism. In high-glucose-treated mesangial cells, CTZ reduced ROSproduction, altered the apoptotic status, and down-regulated transforming growthfactor beta (TGF-) and nuclear factor kappa light chain enhancer of activated B cells(NF-B). Base on the results of our previous and current studies, CTZ decelerationof hyperglycemia-induced DN is attributable to ROS reduction and thereby maintenanceof the mitochondrial function and reduction in TGF- and NF-B levels.


Cilostazol; Diabetic nephropathy; Mesangial cell; Mitochondrial DNA; Oxidative stress
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