title: Local application of sodium thiosulfate prevents cisplatin-induced hearing loss in the guinea pig.
abstract: Cisplatin (CDDP), an anticancer drug used extensively to treat a broad range of neoplasms, has strong ototoxic side effects. Sodium thiosulfate (STS) has been described as a protective agent against CDDP toxicity, but it also reduces CDDP's antitumoral cytotoxicity. To maintain the antitumoral effectiveness of systemic administration of CDDP, a strategy has been developed to apply STS directly into the cochlea. Perfusion of STS into the cochleae of guinea pigs completely prevented CDDP-induced hearing loss, with no change in either compound action potential (CAP) or distortion product otoacoustic emission (DPOAE) audiograms during the time course of the treatment. Histological analysis revealed a minimal loss of outer hair cells (OHCs) in the organ of Corti and no damage to the marginal cells of the stria vascularis as seen in animals exposed to CDDP. Cytocochleograms prepared 6 days after CDDP exposure showed that STS treatment protected more than 92.8% of OHCs and IHCs destined to die. Furthermore, it prevented CDDP-induced mitochondrial damage and subsequent translocation of cytochrome c, DNA fragmentation, and suppressed the apoptotic and necrotic hair cell degeneration. These results suggest that local application of STS may be an interesting strategy to prevent CDDP ototoxicity in patients undergoing CDDP chemotherapy.
authors.affiliation: INSERM-U583, 71, rue de Navacelles, 34090, Montpellier, France.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: R V
authors.initials: RV
authors.lastname: Lloyd Faulconbridge
authors.forename: A
authors.initials: A
authors.lastname: Fetoni
authors.forename: M J
authors.initials: MJ
authors.lastname: Guitton
authors.forename: R
authors.initials: R
authors.lastname: Pujol
authors.forename: J L
authors.initials: JL
authors.lastname: Puel
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002945:Cisplatin / Q000633:toxicity*; D003051:Cochlea / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003574:Cytochrome c Group / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D034381:Hearing Loss / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D015918:Infusion Pumps, Implantable; D009925:Organ of Corti / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013885:Thiosulfates / Q000008:administration & dosage*
chemical_list: D003574:Cytochrome c Group; D013885:Thiosulfates; C017717:sodium thiosulfate; D002945:Cisplatin