Thesis (M.Sc.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology

Cilostazol, a phosphodiesterase- III inhibitor, reportedly exhibits positive effects against Ischemia / reperfusion (I / R) induced injury in several models. However, its potential role against the renal I / R insult has not been elucidated. To test whether the PPAR- Þ (of peroxisome proliferator activated receptor gamma) pathway is involved in the cilostazol effect, rats were randomized into sham, I / R, cilostazol (50 and 100 mg / kg per day, orally), pioglitazone (3 and 10 mg / kg per day, orally) and their combination at the low dose levels. Drugs regimens were administered for 14 days prior to the I/R induction. Pretreatment with cilostazol or pioglitazone provided significant protection against the I/R-induced renal injury as manifested by the attenuated serum levels of creatinine, blood urea nitrogen and cystatin C. Both drugs have also opposed the I/R-induced elevation in tissue contents/activity of neutrophil gelatinase - associated lipocalin (NGAL), kidney injury molecule -1 (Kim -1), nuclear factor- кB, interleukin -18, caspase -1, as well as malondialdehyde, iNOS, myeloperoxidase, ICAM 1 and VCAM 1. Nevertheless, the drugs increased both the PPAR- Þ activity and the content of glutathione

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