The Laryngoscope Lippincott Williams & Wilkins © 2007 The American Laryngological, Rhinological and Otological Society, Inc. Effect Of N-Acetylcysteine on Carboplatin-Induced Ototoxicity and Nitric Oxide Levels in a Rat Model Erdogan Okur, MD; Metin Kilinc, MD; Ilhami Yildirim, MD; M. Akif Kilic, MD; Fatma Inanc Tolun, MD Objective: The aim of the present study is to inves- tigate the effect of N-acetylcysteine (NAC) given 30 min- utes before carboplatin administration on carboplatin- induced ototoxicity and nitric oxide (NO) levels in a rat model. Study Design: Animal study. Methods: Eighteen Sprague-Dawley rats were di- vided into three groups that each contained six animals. Intraperitoneal injection of physiologic saline was per- formed in group 1 twice with an interval of 30 minutes. Group 2 was treated with a single bolus administration of carboplatin at a dose of 256 mg/kg 30 minutes after the intraperitoneal injection of physiologic saline. Group 3 was treated with a single bolus administration of carboplatin at a dose of 256 mg/kg 30 minutes after the intraperitoneal injection of NAC at a dose of 400 mg/kg. Pretreatment and posttreatment distortion product otoacoustic emissions (DPOAE) were per- formed in rats from all groups. Then, the animals were sacrificed on the fourth day, and cochlear tissue NO and glutathione peroxidase (GSH-Px) levels were measured. Results: The comparison of pre- and posttreatment DPOAE responses did not demonstrate any significant changes for groups 1 and 3. Results of group 2 showed a decrease of the DPOAE amplitude. Cochlear NO levels were significantly higher in rats treated with carboplatin than in controls and in those treated with carboplatin plus NAC (P  .05). Cochlear GSH-Px levels were higher in rats treated with carboplatin plus NAC than in those treated with carboplatin, but the difference did not reach statistical significance (P = .079). Conclusions: The present study showed that car- boplatin at higher doses induced hearing loss and in- creased NO levels in the cochlea of rats. NAC appears to have a protective effect against carboplatin-induced oto- toxicity, which may be related to its inhibitory effect on NO production. Key Words: Carboplatin, distortion product oto- acoustic emissions, glutathione peroxidase, nitric oxide, ototoxicity, rat. Laryngoscope, 117:2183–2186, 2007 INTRODUCTION Carboplatin (cis-diammine [1,1-cyclobutanedicarbo xylato]-platinum [II]) is a platinum analogue used in a number of chemotherapeutic regimens for solid tumors such as head and neck, lung, and ovarian carcinomas. 1,2 Carboplatin has an activity profile similar to cisplatin yet possesses an improved toxicity profile that has been at- tributed to greater chemical stability because of slower rates of conversion to active aquated species. 1 On the other hand, a single high dose or repeated doses of carbo- platin chemotherapy have been shown to produce ototox- icity as a side effect in cancer patients. 3–5 Also, it has been shown that carboplatin-induced hearing loss (HL) was related to dose-dependent oxidative injury to the cochlea in a rat model. 6 N-acetylcysteine (NAC) is a cysteine analogue with strong antioxidant activity, which also induces de novo syn- thesis of glutathione (GSH) and which may contribute to long-term protection. 7 NAC was reported to be protective in vitro of outer hair cells (OHC) taken from guinea pigs. 8 Evidence for the involvement of excess nitric oxide (NO) in the modulation of the auditory system has been reported in animals treated with platinum-containing an- ticancer drugs 3 to 4 days posttreatment. 6,9 The aim of the present study is to investigate the effect of NAC, a pre- cursor of GSH and a potent antioxidant, on carboplatin- induced ototoxicity and NO levels in a rat model. MATERIALS AND METHODS Animals Eighteen male Sprague-Dawley rats weighing 170 to 230 g were used in the study. The rats were fed with a standard rat chow and housed under standard controlled temperature (22°  2°C), humidity (40%– 65%), and light (12 hr light/12 hr dark). The From the Departments of Otorhinolaryngology (E.O., I.Y., M.A.K.) and Biochemistry (M.K., F.I.), School of Medicine, Kahramanmaras Sutcu Imam University, Kahramanmaras, Turkey. Editor’s Note: This Manuscript was accepted for publication June 12, 2007. Send correspondence to Dr. Erdog ˘ an Okur, Associate Professor, Kahramanmaras Sutcu Imam University, School of Medicine, Department of Otorhinolaryngology, Hastane Cad. No. 32, 46050 Kahramanmaras, Turkey. E-mail: erdoganokur@yahoo.com DOI: 10.1097/MLG.0b013e31813e6041 Laryngoscope 117: December 2007 Okur et al.: Effect of N-Acetylcysteine on Carboplatin-Induced Ototoxicity 2183