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 r...eceived 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.
