%0 Journal Article
%T Angiotensin Type-1 Receptor Blockade May Not Protect Kidney against Cisplatin-Induced Nephrotoxicity in Rats
%A Roya Rastghalam
%A Mehdi Nematbakhsh
%A Mehrnoosh Bahadorani
%A Fatemeh Eshraghi-Jazi
%A Ardeshir Talebi
%A Maryam Moeini
%A Farzaneh Ashrafi
%A Soheila Shirdavani
%J ISRN Nephrology
%D 2014
%R 10.1155/2014/479645
%X Background. Cisplatin (CDDP) is an anticancer drug, which is accompanied with major side effects including nephrotoxicity. We tested two doses of losartan (10 and 20£¿mg/kg/day) against nephrotoxicity in a rat model treated with daily administration of CDDP (2.5£¿mg/kg/day). Methods. Five groups of rats were examined. Groups 1 and 2 received losartan 10 and 20£¿mg/kg/day, i.p, for a period of 10 days. Group 3 received saline for 10 days, but from day 3 the animals received CDDP (2.5£¿mg/kg/day, i.p) for the next seven days. Groups 4 and 5 received treatment regimen the same as groups 1 and 2, but from day 3 they also received CDDP for the next seven days. At the end of the experiment, blood samples were obtained and the kidneys were removed to undergo pathological investigation and to obtain supernatant from homogenized tissue. Results. CDDP induced nephrotoxicity, but the serum levels of creatinine and blood urea nitrogen were not attenuated by losartan. The pathological findings confirmed that losartan did not have nephroprotective effect in this experimental model. Conclusion. According to the findings, losartan could not improve renal function impaired by toxicity induced by continuous doses of CDDP, and also it worsened the renal failure. 1. Introduction Cisplatin or cis-diamminedichloroplatinum (II) (CDDP) is an anticancer drug for treatment of solid tumors [1, 2]. One of the major side effects of CDDP is nephrotoxicity, which is known as a limitation for CDDP therapy in clinic [3]. CDDP is removed by the kidney by both glomerular filtration and tubular secretion [4]. Inflammation, oxidative stress, and change in the renal circulation may also be induced by CDDP [4¨C6]. To decline CDDP-induced nephrotoxicity, recent studies have concentrated on many supplementations [7¨C11]. Losartan is an angiotensin type-1 receptor blocker as well as an antioxidant, which has been suggested to be nephroprotective against CDDP-induced nephrotoxicity by others [10, 11]. Losartan may reduce renal disease progression in patients with type 2 diabetes [12] and decrease hypertension [13] and microalbuminuria or proteinuria [14, 15]. Several studies have presented different effects of losartan on nephrotoxicity induced by nephrotoxic compounds such as CDDP [10, 11, 16, 17]. Losartan may prevent nephrotoxicity caused by administration of single dose of CDDP in males [11, 16, 17], but it promotes renal damage in females [11]. Although the nephroprotective role of losartan against single dose of CDDP was reported in studies, CDDP is clinically administered sequentially.
%U http://www.hindawi.com/journals/isrn.nephrology/2014/479645/