Cardio-protective effect of cilostazole in a rat model of cardiorenal syndrome type 4

Abstract

The Chronic kidney disease (CKD) is a major health problem . Cardiorenal syndrome (chronic renocardiac syndrome) (CRS) type 4 is gaining a major health concern causing significant morbidity and mortality, putting major burdens on the healthcare system. This study was designed to explore the possible protective effect of cilostazol (phosphodiesterase III inhibitor) versus valsartan ( angiotensin-II receptor blocker ) against CRS type 4 induced by subtotal 5/6 nephrectomy in rats and to explore the underlying mechanisms. Just after surgery, cilostazole (50 and 100mg/kg/day) and valsartan (30mg/kg/day) were given daily by gavage for 10 weeks. Cilostazole treatment significantly improved kidney functions, decreased cardiac malondialdehyde (MDA), nuclear factor kappa B (NFκB), transforming growth factor beta (TGF-ꞵ1), heart weights, heart weight/body weight phosphorylated protein kinase A (p-AKT) , phosphorylated glycogen synthase kinase 3beta (p-GSK3β) levels and serum brain natriuretic peptide (BNP) in 5/6 nephrectomized rats, in addition to significant increase in cardiac levels of superoxide dismutase (SOD), cardiac expressions of peroxisome proliferation-activated receptor gamma (PPARɤ) and endothelial nitric oxide synthase (eNOS) compared to diseased group. Better results were obtained with cilostazole (100 mg/kg/day) pretreated group that were insignificantly different from valsartan pretreated group. Cilostazole has cardioprotective effects in a rat model of CRS type 4. These protective effects are mediated through exerting antiinflammaory, antioxidant , antifibrotic actions , increasing cardiac PPARɤ and eNOS expression as well as abating cardiac hypertrophic signaling pathway .