%0 Journal Article
%T Inhibition of Nitric Oxide Synthase by L-NAME Promotes Cisplatin-Induced Nephrotoxicity in Male Rats
%A Fatemeh Moslemi
%A Mehdi Nematbakhsh
%A Fatemeh Eshraghi-Jazi
%A Ardeshir Talebi
%A Hamid Nasri
%A Farzaneh Ashrafi
%A Maryam Moeini
%A Azam Mansouri
%A Zahra Pezeshki
%J ISRN Toxicology
%D 2013
%R 10.1155/2013/242345
%X Objective. Nitric oxide (NO) has numerous important functions in the kidney. The role of NO in cisplatin (CP)-induced nephrotoxicity is not completely understood. This study was designed to determine the role of NO synthase inhibitor (L-NAME) on the severity of CP-induced nephrotoxicity in rats. Methods. Sixty four male (M) and female (F) Wistar rats were randomly divided into eight groups. The sham groups (group 1, male, and group 2, female, ) received saline. Groups 3 (male, ) and 4 (female, ) were treated with L-NAME (4£¿mg/kg, i.p.), and groups 5 (male, ) and 6 (female, ) received CP (3£¿mg/kg) for 7 days. Groups 7 (male, ) and 8 (female, ) were treated with L-NAME and CP for 7 days. Results. The CP-alone treated rats showed weight loss and increase in serum levels of blood urea nitrogen (BUN) and creatinine (Cr). Coadministration of L-NAME and CP did not improve weight loss, and it increased the levels of BUN and Cr in male but not in female rats ( ). CP alone increased kidney damage significantly ( ), however, the damage induced by combination of CP and L-NAME was gender-related. Conclusion. NOS inhibition by L-NAME increased CP-induced nephrotoxicity, which was gender-related. 1. Introduction Cisplatin (CP) is an effective antineoplastic agent against solid tumors in clinic [1]. Despite the antineoplastic efficacy, the optimal clinical usefulness of CP is usually limited due to its side effects such as nephrotoxicity. CP exerts its nephrotoxic effect mainly in the proximal tubular cells where it is preferentially accumulated [2]. The CP-induced nephrotoxicity may be gender related [3], but the mechanism underlying this sex difference is not understood. Studies have shown that female animals are more sensitive to induce acute renal failure (ARF) [4] and CP enhances urinary sodium excretion in male rats but not in females [5]. Different metabolism and sex hormones [6] may involve in CP-induced nephrotoxicity to be sex related. Nitric oxide (NO) has been suggested to play an important role in CP-induced nephrotoxicity [7, 8]. L-arginine, the precursor of NO, attenuates CP-induced nephrotoxicity in male rats, but it intensifies renal damage induced by CP in female rats [9]. In addition, administration of the nonselective inhibitor of NO synthase, N-nitro L-arginine methyl ester hydrochloride (L-NAME), exacerbates CP-induced nephrotoxicity [10]. The present study was carried out to determine whether administration of L-NAME against nephrotoxicity induced by CP differs between male and female in animal model. 2. Methods and Materials 2.1. Animals
%U http://www.hindawi.com/journals/isrn.toxicology/2013/242345/