Ototoxicity of sodium nitroprusside is not due to nitric oxide

Sodium nitroprusside (SNP) has been used as a donor for nitric oxide (NO) t o study the effects of NO on the mammalian cochlea. In the present study, w e set out to determine whether NO was the chemical responsible for the otot oxic effects seen after the application of SNP at the round window membrane of the adult guinea pig cochlea. In the first instance, NO released from S -nitrosocysteine, a compound not related to cyanide, has no toxic effect on the hair cells of the cochlea. Light-exposed SNP that could no longer prod uce NO, light-exposed SNP to which acetylcysteine (ATC) or hydroxycobalamin (HCL) was added to eliminate cyanide, and freshly prepared SNP to which AT C or HCL was added were also tested. Six groups of animals consisting of th ree animals in each group were used. The single chemical or combination of chemicals stated above was soaked in a piece of gelfoam that was then appli ed to the round window membrane of the animal under ketamine-xylasine anest hesia. The animals were reanesthetized 3 days later and perfused for scanni ng electron microscopy and hair cell quantitative analysis. The results sho wed that, in animals given S-nitrosocysteine, no hair cell loss was noted, while light-exposed SNP led to severe hair cell damage similar to that seen after the administration of fresh SNP, In animals treated with the mixture of light-exposed SNP and ATC or HCL, or fresh SNP with ATC or HCL, ototoxi city was significantly attenuated. These results have convincingly demonstr ated that NO at a certain level is not destructive to auditory hair cells a nd the hair cell loss observed after SNP application is most Likely due to the cyanide released from the SNP instead of NO. (C) 1999 Academic Press.