title: Intervention with cilostazol attenuates renal inflammation in streptozotocin-induced diabetic rats.
abstract: OBJECTIVE
  An inflammatory reaction is commonly found in the pathogenesis of diabetic nephropathy (DN). Cilostazol, a type 3 phosphodiesterase (PDE) inhibitor, has been previously reported to be anti-inflammatory, independent of an anti-platelet property. In the present study, we evaluated the hypothesis that cilostazol has protective effects on diabetic nephropathy by modulating the inflammatory process.
  
  
  METHODS
  Cilostazol was administered (27 or 9 mg kg(-1)d(-1)) to streptozotocin (STZ)-induced diabetic rats for eight weeks. We studied the kidney expression of vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1 by immunofluorescence, western blotting and real-time PCR. The renal monocyte chemoattractant protein (MCP)-1 and vascular endothelial growth factor (VEGF) levels were examined by ELISA. The nuclear factor (NF)-kappaB-DNA binding activity was assessed by electrophoresis mobility shift assay (EMSA).
  
  
  RESULTS
  Our results showed cilostazol inhibited diabetes-induced hypertrophy of the glomeruli and infiltration of inflammatory cells, as well as the increase in the VCAM-1 and ICAM-1 mRNA and protein expression, and MCP-1 and VEGF contents in the kidneys. Consistent with these findings, cilostazol attenuated the enhanced activation of NF-kappaB in diabetic rats.
  
  
  CONCLUSIONS
  These results demonstrate that the renoprotective effects of cilostazol may be mediated by its anti-inflammatory actions, including inhibition of NF-kappaB activation and the subsequent decrease in proinflammatory factors, such as VCAM-1, ICAM-1, MCP-1 and VEGF expression in kidneys of diabetic rats.
authors.affiliation: Shandong Provincial Hospital, Shandong University, Jinan, China.
authors.forename: Furong
authors.initials: F
authors.lastname: Wang
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.forename: Lin
authors.initials: L
authors.lastname: Cheng
authors.forename: Tingguo
authors.initials: T
authors.lastname: Zhang
authors.forename: Jianting
authors.initials: J
authors.lastname: Hu
authors.forename: Mingfeng
authors.initials: M
authors.lastname: Cao
authors.forename: Jiajun
authors.initials: J
authors.lastname: Zhao
authors.forename: Ruichen
authors.initials: R
authors.lastname: Guo
authors.forename: Ling
authors.initials: L
authors.lastname: Gao
authors.forename: Xiumei
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D018932:Chemokine CCL2 / Q000096:biosynthesis; D000077407:Cilostazol; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003928:Diabetic Nephropathies / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007668:Kidney / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000096:biosynthesis; D009393:Nephritis / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D016328:NF-kappa B; D013777:Tetrazoles; D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D018799:Intercellular Adhesion Molecule-1; D013311:Streptozocin; D000077407:Cilostazol