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


METHODS
Experimental study.


METHODS
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.


METHODS
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.
Saliba
Issam
I
Department of Otorhinolaryngology-Head and Neck Surgery, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec. issam.saliba@umontreal.ca
El Fata
Fouad
F
Ouelette
Valérie
V
Robitaille
Yves
Y
D000111:Acetylcysteine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D002945:Cisplatin / Q000009:adverse effects*; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D006168:Guinea Pigs; D006311:Hearing Disorders / Q000139:chemically induced* / Q000175:diagnosis / Q000517:prevention & control*; D007267:Injections; D008775:Methylprednisolone / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014432:Tympanic Membrane / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D002945:Cisplatin; D000111:Acetylcysteine; D008775:Methylprednisolone