Transtympanic Ringer's lactate application in the prevention of cisplatinum-induced ototoxicity in a chinchilla animal model.
OBJECTIVE
Ototoxicity is currently the most frequent dose-limiting side effect of cisplatinum chemotherapy. To date, there is no protocol to prevent dose-related ototoxicity, despite its prevalence and predictability. Previous animal studies have found lactate to be effective in the prevention of cisplatinum-induced ototoxicity. The objective of this study was to test the protective benefits of transtympanic Ringer's lactate in the prevention of cisplatinum-induced ototoxicity.


METHODS
A randomized prospective controlled trial was conducted in an animal model.


METHODS
Animal care research facilities of The Montreal Children's Hospital Research Institute.


METHODS
A total of 44 chinchillas were exposed to systemic cisplatinum injected intraperitoneally in divided cycles to reach the targeted cumulative dosage of 16 mg/kg. Ototopical application of Ringer's lactate solution 0.2 mL twice per day during the chemotherapy cycles was performed. Each animal had one experimental (Ringer's) and one control ear. Distortion product otoacoustic emissions (DPOAEs) were collected for a wide range of frequencies (between 1 and 16 kHz), and scanning electron microscopy was performed to evaluate the protective effects of Ringer's lactate.


RESULTS
Ototopical application of Ringer's lactate solution in our established chinchilla animal model did not provide an otoprotective effect as measured by the DPOAE response and electron microscopy.


CONCLUSIONS
In our study, the intratympanic application of Ringer's lactate solution through a tympanostomy ventilation tube did not provide an otoprotective effect. Further studies are needed to better assess the otoprotective or ototoxic effects of Ringer's lactate and other antioxidants on animal and human hearing.
Munguia
Raymundo
R
McGill Auditory Sciences Laboratory, The Montreal Children's Hospital, Montreal, Quebec, Canada.
Sahmkow
Sofia I
SI
Funnell
W Robert J
WR
Daniel
Sam J
SJ
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002682:Chinchilla; D002945:Cisplatin / Q000009:adverse effects*; D003051:Cochlea / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004427:Ear Diseases / Q000139:chemically induced* / Q000175:diagnosis / Q000517:prevention & control*; D005260:Female; D006198:Hair Cells, Auditory / Q000187:drug effects; D007552:Isotonic Solutions / Q000008:administration & dosage*; D008876:Middle Ear Ventilation; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects*; D000077325:Ringer's Lactate
D000970:Antineoplastic Agents; D007552:Isotonic Solutions; D000077325:Ringer's Lactate; D002945:Cisplatin