Role of reactive radicals in degeneration of the auditory system of mice following cisplatin treatment.

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. 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. 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. The hydroxyl radical may be a critical target for a strategy aimed at protecting auditory function from cisplatin toxicity.