title: Prevention of cisplatin-induced hearing loss by administration of a thiosulfate-containing gel to the middle ear in a guinea pig model.
abstract: OBJECTIVE
  Thiosulfate may reduce cisplatin-induced ototoxicity, most likely by relieving oxidative stress and by forming inactive platinum complexes. This study aimed to determine the concentration and protective effect of thiosulfate in the cochlea after application of a thiosulfate-containing high viscosity formulation of sodium hyaluronan (HYA gel) to the middle ear prior to i.v. injection of cisplatin in a guinea pig model.
  
  
  METHODS
  The release of thiosulfate (0.1 M) from HYA gel (0.5% w/w) was explored in vitro. Thiosulfate in the scala tympani perilymph of the cochlea 1 and 3 h after application of thiosulfate in HYA gel to the middle ear was quantified with HPLC and fluorescence detection. Thiosulfate in blood and CSF was also explored. The potential otoprotective effect was evaluated by hair cell count after treatment with thiosulfate in HYA gel applied to the middle ear 3 h prior to cisplatin injection (8 mg/kg b.w.).
  
  
  RESULTS
  HYA did not impede the release of thiosulfate. Middle ear administration of thiosulfate in HYA gel gave high concentrations in the scala tympani perilymph while maintaining low levels in blood, and it protected against cisplatin-induced hair cell loss.
  
  
  CONCLUSIONS
  HYA gel is an effective vehicle for administration of thiosulfate to the middle ear. Local application of a thiosulfate-containing HYA gel reduces the ototoxicity of cisplatin most likely without compromising its antineoplastic effect. This provides a minimally invasive protective treatment that can easily be repeated if necessary.
authors.affiliation: Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden. cecilia.engmer-berglin@karolinska.se
authors.forename: Cecilia Engmér
authors.initials: CE
authors.lastname: Berglin
authors.forename: Pernilla Videhult
authors.initials: PV
authors.lastname: Pierre
authors.forename: Tobias
authors.initials: T
authors.lastname: Bramer
authors.forename: Katarina
authors.initials: K
authors.lastname: Edsman
authors.forename: Hans
authors.initials: H
authors.lastname: Ehrsson
authors.forename: Staffan
authors.initials: S
authors.lastname: Eksborg
authors.forename: Göran
authors.initials: G
authors.lastname: Laurell
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D002945:Cisplatin / Q000633:toxicity*; D004432:Ear, Middle / Q000187:drug effects*; D005260:Female; D005782:Gels; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects; D034381:Hearing Loss / Q000139:chemically induced / Q000517:prevention & control*; D006820:Hyaluronic Acid / Q000008:administration & dosage*; D008297:Male; D013885:Thiosulfates / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D005782:Gels; D013885:Thiosulfates; D006820:Hyaluronic Acid; D002945:Cisplatin