RGD Reference Report - Intervention with cilostazol attenuates renal inflammation in streptozotocin-induced diabetic rats. - Rat Genome Database

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Intervention with cilostazol attenuates renal inflammation in streptozotocin-induced diabetic rats.

Authors: Wang, F  Li, M  Cheng, L  Zhang, T  Hu, J  Cao, M  Zhao, J  Guo, R  Gao, L  Zhang, X 
Citation: Wang F, etal., Life Sci. 2008 Dec 19;83(25-26):828-35. Epub 2008 Oct 21.
RGD ID: 2312764
Pubmed: PMID:18983856   (View Abstract at PubMed)
DOI: DOI:10.1016/j.lfs.2008.09.027   (Journal Full-text)

AIMS: 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. MAIN 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). KEY FINDINGS: 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. SIGNIFICANCE: 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Diabetes Mellitus  ISOVcam1 (Rattus norvegicus)2312764; 2312764mRNA and protein:increased expression:kidneyRGD 
Experimental Diabetes Mellitus  IEP 2312764mRNA and protein:increased expression:kidneyRGD 

Objects Annotated

Genes (Rattus norvegicus)
Vcam1  (vascular cell adhesion molecule 1)

Genes (Mus musculus)
Vcam1  (vascular cell adhesion molecule 1)

Genes (Homo sapiens)
VCAM1  (vascular cell adhesion molecule 1)


Additional Information