Le rôle du lactate et du N-acétylcystéine 
intra-tympanique dans la prévention de l’ototoxicité secondaire au cisplatin
Objectives There is no approved agent to prevent cisplatin-induced ototoxicity. Our objectives are to identify and compare the protective effect of intratympanic injections of lactate or N-acetylcysteine (NAC) in the prevention of cisplatin-induced ototoxicity and to study systemic diffusion of intratympanic NAC.  Methods Sixteen guinea pigs, forming two groups, received respectively intratympanic lactate and 20% NAC in one ear. The contra-lateral ears received a control saline solution. After 30 minutes, an intra-peritoneal cisplatin injection of 3 mg/kg was performed and repeated once a week to achieve a final dose of 24mg/kg. Auditory brainstem responses (ABR) were recorded before any injection, after 9mg/kg and after 24mg/kg of cisplatin for the frequencies 2, 4, 6 and 8kHz. Cochleas were analyzed under scanning electron microscope. Systemic diffusion of NAC was studied using high performance liquid chromatography.  Results For the control ears, ABR thresholds increased uniformly by an average of 28.4dB. The lactate group showed a lower threshold increase by an average of 17.0dB. The NAC showed an important threshold increase of 89.0dB. Lactate showed a significant hearing protection at 2000Hz (p<0.01). Electron microscopy revealed partial preservation of cochlear outer hair cells stereocilia for the ears treated with lactate and severe disruption for NAC group. No systemic diffusion of NAC was observed with chromatography. Conclusion Lactate offers significant partial protection against cisplatin-induced ototoxicity. NAC does not offer any protection when administered in high concentrations. Intratympanic NAC does not diffuse systemically.
Cisplatin Cisplatin Ototoxicity Intra-tympanic Transtympanic Lactate Lactate N-acetylcysteine Chromatography Electronic microscopy