Cilostazol Renoprotective Effect: Modulation of PPAR-γ, NGAL, KIM-1 and IL-18 Underlies Its Novel Effect in a Model of Ischemia-Reperfusion

摘要: Cilostazol, a phosphodiesterase-III inhibitor, reportedly exhibits positive effects against ischemia/reperfusion (I/R)-induced injury in several models. However, its potential role the renal I/R insult has not been elucidated. To test whether PPAR-γ (of peroxisome proliferator activated receptor gamma) pathway is involved cilostazol effect, rats were randomized into sham, I/R, (50 and 100 mg/kg per day, orally), pioglitazone (3 10 orally) their combination at low dose levels. Drugs regimens administered for 14 days prior to induction. Pretreatment with or provided significant protection I/R-induced as manifested by attenuated serum levels of creatinine, blood urea nitrogen cystatin C. Both drugs have also opposed elevation tissue contents/activity neutrophil gelatinase-associated lipocalin (NGAL), kidney molecule-1 (Κim-1), nuclear factor-κB, interleuκin-18, caspase-1, well malondialdehyde, iNOS, myeloperoxidase, ICAM-1 VCAM-1. Nevertheless, increased both transcriptional activity content glutathione. Furthermore, combining two doses produced comparable that high level either drug, advocating fortification renoprotective effect when given concomitantly cilostazol. In conclusion, purveyed conceivable novel mechanisms alleviated incidents associated acute alone partially via besides amendment aforementioned biomarkers.