The role of intratympanic lactate injection in the prevention of cisplatin-induced ototoxicity.
OBJECTIVE
There is no approved agent to prevent cisplatin-induced ototoxicity. Our objectives were to: 1) identify and compare the effect of intratympanic injections of lactate or N-acetylcysteine (NAC) in the prevention of cisplatin-induced ototoxicity, 2) investigate inner ear protection using a scanning electron microscope, and 3) study systemic diffusion of intratympanic NAC.


METHODS
Prospective animal study.


METHODS
Sixteen guinea pigs formed two groups, and respectively received intratympanic lactate and 20% NAC in one ear. The contralateral ears received a control saline solution. After 30 minutes, an intraperitoneal cisplatin injection of 3 mg/kg was performed and repeated eight times, once a week, to achieve 24 mg/kg. Auditory brainstem responses (ABRs) were recorded before any injection, after 9 mg/kg and after 24 mg/kg of cisplatin for the frequencies 2, 4, 6 and 8 kHz. 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 and averaged 28.4 dB. The lactate group showed a lower threshold increase and averaged 17.0 dB. The NAC showed an important threshold increase of 89.0 dB. Lactate showed a significant hearing protection at 2000 Hz (P < .01). Electron microscopy revealed partial preservation of outer hair cell stereocilia for the ears treated with lactate and severe disruption for NAC group. No systemic diffusion of NAC was observed with chromatography.


CONCLUSIONS
Intratympanic lactate offers significant partial protection against cisplatin-induced ototoxicity at midfrequencies. High-concentration NAC does not seem a viable solution as it causes a considerable inflammatory reaction. NAC does not diffuse systemically.
Nader
Marc-Elie
ME
Department of Otolaryngology-Head and Neck Surgery, Sainte-Justine University Hospital Center, Montreal University, Montreal, Quebec, Canada.
Théorêt
Yves
Y
Saliba
Issam
I
D000111:Acetylcysteine / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D002945:Cisplatin / Q000633:toxicity*; D006168:Guinea Pigs; D034381:Hearing Loss / Q000139:chemically induced* / Q000517:prevention & control*; D007773:Lactates / Q000008:administration & dosage* / Q000494:pharmacology; D008855:Microscopy, Electron, Scanning; D011446:Prospective Studies; D018709:Statistics, Nonparametric; D014432:Tympanic Membrane
D007773:Lactates; D002945:Cisplatin; D000111:Acetylcysteine