Protective effect of metformin against cisplatin-induced ototoxicity in an auditory cell line

Jiwon Chang, Hak Hyun Jung, Ji Yoon Yang, Sehee Lee, June Choi, Gi Jung Im, Sung Won Chae

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24 Citations (Scopus)

Abstract

Metformin, an antidiabetic drug with potent anticancer activity, is known to prevent oxidative stress-induced cell death in several cell types through a mechanism dependent on the mitochondria. In the present study, we investigated the influence of metformin on cisplatin ototoxicity in an auditory cell line. Cell viability was determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazoliumbromide (Sigma, St. Louis, MO, USA) cell proliferation assay. Oxidative stress and apoptosis were assessed by flow cytometry analysis, Hoechst 33258 staining, reactive oxygen species (ROS) measurement, and western blotting. Intracellular calcium concentration changes were detected using calcium imaging. Pretreatment with 1 mM metformin prior to the application of 20 μM cisplatin significantly decreased the frequency of late apoptosis in HEI-OC1 cells and also significantly attenuated the cisplatin-induced increase in ROS. In addition, metformin inhibited the activation of caspase-3 and levels of poly-ADP-ribose polymerase (PARP). Pretreatment with metformin prevented the cisplatin-induced elevation in intracellular calcium concentrations. We propose that metformin protects against cisplatin-induced ototoxicity by inhibiting the increase in intracellular calcium levels, preventing apoptosis, and limiting ROS production.

Original languageEnglish
Pages (from-to)149-158
Number of pages10
JournalJARO - Journal of the Association for Research in Otolaryngology
Volume15
Issue number2
DOIs
Publication statusPublished - 2014 Apr

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Keywords

  • calcium imaging
  • cell culture
  • cisplatin
  • metformin
  • ototoxicity

ASJC Scopus subject areas

  • Otorhinolaryngology
  • Sensory Systems

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