Role of reactive radicals in degeneration of the auditory system of mice following cisplatin treatment.
OBJECTIVE
It has been suggested that reactive radical species are involved in the mechanism of cisplatin-induced hearing loss. However, the nature of the free radicals involved is not fully understood. We examined the effects of two highly reactive species, hydroxyl radicals and peroxynitrite, on the auditory system of mice following cisplatin treatment.


METHODS
Expression of 4-hydroxynonenal (HNE), a marker of lipid peroxidation by the hydroxyl radical, and nitrotyrosine (NT), a marker for protein peroxidation by peroxynitrite, was examined immunohistochemically in mouse cochleae injured by means of local application of cisplatin.


RESULTS
Loss of outer hair cells (OHCs) and spiral ganglia was found in cochleae affected by cisplatin. Both HNE and NT were detected in auditory epithelia and neurons damaged by cisplatin. Interestingly, auditory hair cells produced HNE, but not NT. Our findings indicate contributions by both HNE and NT to the degeneration of the auditory system due to cisplatin, and a crucial role of the hydroxyl radical in degeneration of OHCs.


CONCLUSIONS
The hydroxyl radical may be a critical target for a strategy aimed at protecting auditory function from cisplatin toxicity.
Lee
Ji Eun
JE
Department of Otolaryngology--Head and Neck Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Nakagawa
Takayuki
T
Kim
Tae Soo
TS
Endo
Tsuyoshi
T
Shiga
Atsushi
A
Iguchi
Fukuichiro
F
Lee
Sang Heun
SH
Ito
Juichi
J
D000447:Aldehydes / Q000032:analysis; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D002945:Cisplatin / Q000633:toxicity*; D003051:Cochlea / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005609:Free Radicals / Q000378:metabolism*; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017665:Hydroxyl Radical / Q000378:metabolism; D007150:Immunohistochemistry; D015227:Lipid Peroxidation; D051379:Mice; D008810:Mice, Inbred C57BL; D030421:Peroxynitrous Acid / Q000378:metabolism; D013136:Spiral Ganglion / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis
D000447:Aldehydes; D000970:Antineoplastic Agents; D005609:Free Radicals; D030421:Peroxynitrous Acid; D017665:Hydroxyl Radical; C002744:3-nitrotyrosine; D014443:Tyrosine; C027576:4-hydroxy-2-nonenal; D002945:Cisplatin