title: Safety and otoprotection of metformin in radiation-induced sensorineural hearing loss in the guinea pig.
abstract: OBJECTIVE
  There is currently no treatment available to prevent radiation-induced sensorineural hearing loss. Metformin has antineoplastic effects and is able to regulate the mitochondrial production of reactive oxygen species after cellular stress, which is one of the mechanisms involved in apoptosis after radiation damage. The objective of this study was to determine the safety and radioprotective properties of metformin against radiation-induced cochlear damage both in vitro and in vivo.
  
  
  METHODS
  In vitro and prospective animal study.
  
  
  METHODS
  Animal Care Facilities of the Montreal Children's Hospital Research Institute.
  
  
  METHODS
  Cultured auditory hair cells (HEI-OC1) were exposed to different concentrations of metformin to determine its safety. Cells were incubated with different metformin concentrations and subjected to radiation. Cell viability after experiments was determined with the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Sixteen guinea pigs were divided in 2 groups: drinking tap water (n = 8) and drinking water containing metformin (n = 8). The animals were unilaterally irradiated for 20 days (total dose 70 Gy), and the ears were divided in 4 groups: control (n = 8), irradiated (n = 8), metformin (n = 8), and experimental (n = 8). Auditory brainstem responses were assessed before and 1, 6, and 16 weeks after completion of radiotherapy.
  
  
  RESULTS
  Metformin was not cytotoxic or radioprotective in cultured auditory hair cells. Experimental ears had less hearing loss than radiated ones; however, differences were not statistically significant (P > .05).
  
  
  CONCLUSIONS
  Metformin is not ototoxic or radioprotective in vitro or in vivo. Ears solely subjected to metformin had better hearing thresholds than the rest of the groups.
authors: McGill Auditory Sciences Laboratory, Montréal, Quebec, Canada.
authors: Mario A
authors: MA
authors: Mujica-Mota
authors: Pezhman
authors: P
authors: Salehi
authors: Slobodan
authors: S
authors: Devic
authors: Sam J
authors: SJ
authors: Daniel
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects*; D006319:Hearing Loss, Sensorineural / Q000188:drug therapy* / Q000209:etiology*; D008687:Metformin / Q000494:pharmacology*; D011446:Prospective Studies; D011878:Radiotherapy / Q000009:adverse effects*
chemical_list: D008687:Metformin
keywords: Metformin; cell line; radiation; radioprotection; sensorineural hearing loss