Round window application of D-methionine, sodium thiosulfate, brain-derived neurotrophic factor, and fibroblast growth factor-2 in cisplatin-induced ototoxicity.
OBJECTIVE
In this study we tested the effect of local administration of D-methionine, sodium thiosulfate, brain-derived neurotrophic factor, and fibroblast growth factor-2 on cisplatin ototoxicity in guinea pigs to the round window membrane.


BACKGROUND
Cisplatin is an important antineoplastic agent in the therapy of many malignancies. Its clinical utility is limited by severe side effects, including ototoxicity. Recent studies have shown protection against cisplatin ototoxicity in animal experiments by the systemic administration of D-methionine and sodium thiosulfate. Growth factors such as brain-derived neurotrophic factor and fibroblast growth factor-2 also have shown otoprotective effects in in vitro studies.


METHODS
Osmotic pumps (Alzet) were implanted unilaterally in 30 guinea pigs. Five groups of six animals received either D-methionine, sodium thiosulfate, fibroblast growth factor-2, brain-derived neurotrophic factor, or saline 0.9%. Cisplatin was administered intraperitoneally for 5 consecutive days. Distortion product otoacoustic emissions were recorded every day. The animals were killed on day 6, and their cochleae were removed and analyzed by transmission electron microscopy.


RESULTS
Compared with control animals, guinea pigs treated with D-methionine showed better otoacoustic emissions on days 3 and 4 (Mann-Whitney test, p < 0.05). The differences were not evident on days 5 and 6. Sodium thiosulfate, brain-derived neurotrophic factor, and fibroblast growth factor-2 showed no significant protective effect.


CONCLUSIONS
Local application to the round window membrane can be used as an effective treatment in the prevention of cisplatin toxicity. Local application may avoid systemic side effects and reduce the antineoplastic effects of cisplatin.
Wimmer
Christoph
C
Department of Otorhinolaryngology, Head and Neck Surgery, University of Munich, Germany. christoph.wimmer@hno.med.uni-muenchen.de
Mees
Klaus
K
Stumpf
Peter
P
Welsch
Ulrich
U
Reichel
Oliver
O
Suckfüll
Markus
M
D000287:Administration, Topical; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage*; D002945:Cisplatin / Q000009:adverse effects*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage*; D006168:Guinea Pigs; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced / Q000517:prevention & control*; D007260:Infusion Pumps; D008715:Methionine / Q000008:administration & dosage*; D017084:Otoacoustic Emissions, Spontaneous; D012044:Regression Analysis; D012405:Round Window, Ear; D013885:Thiosulfates / Q000008:administration & dosage*
D000970:Antineoplastic Agents; D019208:Brain-Derived Neurotrophic Factor; D013885:Thiosulfates; D016222:Fibroblast Growth Factor 2; D008715:Methionine; C017717:sodium thiosulfate; D002945:Cisplatin