title: Ototoxicity of sodium nitroprusside is not due to nitric oxide.
abstract: Sodium nitroprusside (SNP) has been used as a donor for nitric oxide (NO) to study the effects of NO on the mammalian cochlea. In the present study, we set out to determine whether NO was the chemical responsible for the ototoxic 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 produce NO, light-exposed SNP to which acetylcysteine (ATC) or hydroxycobalamin (HCL) was added to eliminate cyanide, and freshly prepared SNP to which ATC or HCL was added were also tested. Six groups of animals consisting of three 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 applied to the round window membrane of the animal under ketamine-xylasine anesthesia. The animals were reanesthetized 3 days later and perfused for scanning electron microscopy and hair cell quantitative analysis. The results showed 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, ototoxicity was significantly attenuated. These results have convincingly demonstrated that NO at a certain level is not destructive to auditory hair cells and the hair cell loss observed after SNP application is most likely due to the cyanide released from the SNP instead of NO.
authors.affiliation: Department of Otolaryngology, National University Hospital, Singapore.
authors.forename: R S
authors.initials: RS
authors.lastname: Ruan
authors.forename: S K
authors.initials: SK
authors.lastname: Leong
authors.forename: K H
authors.initials: KH
authors.lastname: Yeoh
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000648:ultrastructure; D006397:Hematinics / Q000494:pharmacology; D006879:Hydroxocobalamin / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000009:adverse effects*; D012405:Round Window, Ear / Q000187:drug effects* / Q000648:ultrastructure; D014665:Vasodilator Agents / Q000009:adverse effects*
chemical_list: D016166:Free Radical Scavengers; D006397:Hematinics; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D006879:Hydroxocobalamin; D000111:Acetylcysteine