Cancer Chemotherapy and Pharmacology

, Volume 68, Issue 6, pp 1547–1556

Prevention of cisplatin-induced hearing loss by administration of a thiosulfate-containing gel to the middle ear in a guinea pig model

  • Cecilia Engmér Berglin
  • Pernilla Videhult Pierre
  • Tobias Bramer
  • Katarina Edsman
  • Hans Ehrsson
  • Staffan Eksborg
  • Göran Laurell
Original Article

Abstract

Purpose

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.

Conclusion

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.

Keywords

Cisplatin Thiosulfate Sodium hyaluronan Topical administration Guinea pig Ototoxicity 

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Cecilia Engmér Berglin
    • 1
    • 2
  • Pernilla Videhult Pierre
    • 3
  • Tobias Bramer
    • 4
  • Katarina Edsman
    • 4
  • Hans Ehrsson
    • 3
  • Staffan Eksborg
    • 5
  • Göran Laurell
    • 6
  1. 1.Department of Clinical Science, Intervention and TechnologyKarolinska InstitutetStockholmSweden
  2. 2.Department of OtorhinolaryngologyKarolinska University HospitalStockholmSweden
  3. 3.Department of Oncology-PathologyKarolinska InstitutetStockholmSweden
  4. 4.Department of PharmacyUppsala UniversityUppsalaSweden
  5. 5.Department of Woman and Child HealthKarolinska InstitutetStockholmSweden
  6. 6.Department of Clinical ScienceUmeå UniversityUmeåSweden

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