Are intratympanic injections of N-acetylcysteine and methylprednisolone protective against Cisplatin-induced ototoxicity?

Author(s): Saliba I, El Fata F, Ouelette V, Robitaille Y

Affiliation(s): Department of Otorhinolaryngology-Head and Neck Surgery, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec. issam.saliba@umontreal.ca

Publication date & source: 2010-06, J Otolaryngol Head Neck Surg., 39(3):236-43.

OBJECTIVE: To identify and to compare the protective effect of intratympanic injections of N-acetylcysteine (NAC) or methylprednisolone to prevent cisplatin-induced ototoxicity, to investigate inner ear protection using an electron microscope and to evaluate the effect of 4% NAC on the middle ear. DESIGN: Experimental study. SETTING: Basic ear research center at Sainte-Justine hospital. METHODS: Ten Hartley guinea pigs were divided into two groups, according to the product used intratympanically (4% NAC or 62.5 mg/mL methylprednisolone) in one ear. The other ear was left as control. Cisplatin was administered intraperitoneally (3 mg/kg), once a week for 5 weeks. MAIN OUTCOME MEASURES: Auditory evoked brainstem responses were used to test hearing. The inner ear was screened using an electron microscope. RESULTS: Significant threshold shift was seen on all tested frequencies of both groups. This difference is clinically and statistically significant in the methylprednisolone group. The NAC-treated group had a lower threshold shift than the methylprednisolone group in both ears. Electron microscope studies showed in all untreated-NAC ears severe lesion of the inner and outer hair cells with complete degeneration of steriocilia, whereas in NAC-treated ears we noted a nuclear and cytoplasmic membrane preservation with some preservation of steriocila. Also, 4% intratympanic NAC produces an external auditory canal and middle ear inflammatory reaction. CONCLUSIONS: Intratympanic injections of methylprednisolone failed to demonstrate efficacy in protecting cisplatin ototoxicity whereas 4% NAC showed a partial protection. The safety of intratympanic injections should be investigated in further studies, as possible systemic shift of the locally administered treatment is suspected.