Effect of N-acetylcysteine on carboplatin-induced ototoxicity and nitric oxide levels in a rat model.
OBJECTIVE
The aim of the present study is to investigate the effect of N-acetylcysteine (NAC) given 30 minutes before carboplatin administration on carboplatin-induced ototoxicity and nitric oxide (NO) levels in a rat model.


METHODS
Animal study.


METHODS
Eighteen Sprague-Dawley rats were divided into three groups that each contained six animals. Intraperitoneal injection of physiologic saline was performed 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 performed 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 carboplatin at higher doses induced hearing loss and increased NO levels in the cochlea of rats. NAC appears to have a protective effect against carboplatin-induced ototoxicity, which may be related to its inhibitory effect on NO production.
Okur
Erdogan
E
Department of Otorhinolaryngology, School of Medicine, Kahramanmaras Sutcu Imam University, Kahramanmaras, Turkey. erdoganokur@yahoo.com
Kilinc
Metin
M
Yildirim
Ilhami
I
Kilic
M Akif
MA
Tolun
Fatma Inanc
FI
D000111:Acetylcysteine / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity; D015415:Biomarkers / Q000378:metabolism; D016190:Carboplatin / Q000633:toxicity; D003051:Cochlea / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem; D005500:Follow-Up Studies; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013053:Spectrophotometry; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D015415:Biomarkers; D016166:Free Radical Scavengers; D009569:Nitric Oxide; D016190:Carboplatin; D005979:Glutathione Peroxidase; D000111:Acetylcysteine