Protektivni efekti kvercetina i aminogvanidina kod pacova sa akutnom bubrežnom insuficijencijom izazvanom cisplatinom

Abstract

Cisplatin has a significant therapeutic effects in treatmen of different types of cancers. Its usefulness is limited by side effects, particularly nephrotoxicity. Quercetin is natural flavonoid which protects membrane lipids, nuclear DNA and proteins, from oxidative damage through its strong capacity to inhibit oxidative stress and inflammation. Aminoguanidine is an inhibitor of inducible nitric oxide synthase which inhibits generating of nitric oxide and reacts with peroxynitrite. The aim of this study was to investigate the mechanism of cisplatin nephrotoxicity and protective effects of quercetin and aminoguanidine on cisplatin-induced nephrotoxicity in rats. Experiments were done on 48 Wistar rats divided into 6 groups of 8 animals each. The control group received saline (1 ml/day) intraperitoneally (i.p.) for 9 days. Animals in the Q and AG groups, serving as positive controls, received quercetin i.p. (50 mg/kg) and aminoguanidine i.p. (100 mg/kg) for 9 days. CIS group received cisplatin in a single dose of 8 mg/kg i.p. Animals in CISQ group received the same dose of cisplatin and quercetin (50 mg/kg) i.p. for 9 days. Animals in CISAG group received the same dose of cisplatin and aminoguanidine (100 mg/kg) i.p. for nine days. Quantitative evaluation of cisplatin-induced structural and functional alterations of kidneys was performed by histopathological, biochemical and morphometric analyses. Treatment with cisplatin caused a severe nephrotoxicity which was evidenced by an elevation of serum urea and creatinine levels. The significant increase in malondialdehyde levels and advanced oxidative protein products and decrease of catalase in kidneys of rats in CIS group indicated that one of mechanisms of cisplatin nephrotoxicity is mediated through oxidative stress. Ultrastrucural changes in kidney after cisplatin treatment included enlargement of glomeruli, infiltration, thickened of glomerular basement membrane and oedema and vacuolization of tubular cells. Quercetin and aminoguainidene administration protected kidney tissue against the oxidative damage and the nephrotoxic effect caused by cisplatin. The results from our study indicate that quercetin and aminoguanidine attenuate oxidative-stress in cisplatinn-treated rats and signicicantly reduce morphological and functional kidney alterations induced by cisplatin.