Metformin protects against gentamicin-induced hair cell death in vitro but not ototoxicity in vivo

Naoki Oishi, Ann Kendall, Jochen Schacht

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Metformin (N,N-dimethylbiguanidine) is a widely employed oral hypoglycemic agent for the management of type 2 diabetes mellitus. Its antioxidant properties and safe clinical use raise the possibility of preventing gentamicin-induced hearing loss in patients. Therefore, we screened the usefulness of metformin against gentamicin toxicity in murine cochlear explants and in the guinea pig in vivo. We confirmed in organ culture that metformin blocks the gentamicin-induced translocation of endonuclease G into the nucleus of outer hair cells and attenuates hair cell loss. In vivo, gentamicin treatment with 80, 100, or 130 mg/kg body weight for 14 days induced significant threshold shifts as determined by auditory brain stem responses. Metformin (30, 75, or 100 mg/kg for 14 days) was well tolerated without any indication of auditory side effects. However, co-administration of metformin with gentamicin in various permutations did not prevent loss of auditory function. On the contrary, combined treatment at higher dosages aggravated the gentamicin-induced threshold shifts and caused additional adverse reactions including body weight loss and premature deaths in some animals. These results caution against the use of metformin co-treatment with aminoglycosides and confirm the need for in vivo studies in order to evaluate potentially protective agents selected by in vitro screens.

Original languageEnglish
Pages (from-to)65-69
Number of pages5
JournalNeuroscience Letters
Volume583
DOIs
Publication statusPublished - 2014 Nov 7

Keywords

  • Cochlear explants
  • Gentamicin
  • Guinea pigs
  • Metformin
  • Ototoxicity
  • Outer hair cells

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Metformin protects against gentamicin-induced hair cell death in vitro but not ototoxicity in vivo'. Together they form a unique fingerprint.

  • Cite this