Protective role of Nrf2 in age-related hearing loss and gentamicin ototoxicity

Tomofumi Hoshino, Keiji Tabuchi, Bungo Nishimura, Shuho Tanaka, Masahiro Nakayama, Tetsuro Ishii, Eiji Warabi, Toru Yanagawa, Ritsuku Shimizu, Masayuki Yamamoto, Akira Hara

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58 Citations (Scopus)


Expression of antioxidant enzymes is regulated by transcription factor NF-E2-related factor (Nrf2) and induced by oxidative stress. Reactive oxygen species contribute to the formation of several types of cochlear injuries, including age-related hearing loss and gentamicin ototoxicity. In this study, we examined the roles of Nrf2 in age-related hearing loss and gentamicin ototoxicity by measuring auditory brainstem response thresholds in Nrf2-knockout mice. Although Nrf2-knockout mice maintained normal auditory thresholds at 3. months of age, their hearing ability was significantly more impaired than that of age-matched wild-type mice at 6 and 11. months of age. Additionally, the numbers of hair cells and spiral ganglion cells were remarkably reduced in Nrf2-knockout mice at 11. months of age. To examine the importance of Nrf2 in protecting against gentamicin-induced ototoxicity, 3-day-old mouse organ of Corti explants were cultured with gentamicin. Hair cell loss caused by gentamicin treatment was enhanced in the Nrf2-deficient tissues. Furthermore, the expressions of some Nrf2-target genes were activated by gentamicin treatment in wild-type mice but not in Nrf2-knockout mice. The present findings indicate that Nrf2 protects the inner ear against age-related hearing injuries and gentamicin ototoxicity by up-regulating antioxidant enzymes and detoxifying proteins.

Original languageEnglish
Pages (from-to)94-98
Number of pages5
JournalBiochemical and Biophysical Research Communications
Issue number1
Publication statusPublished - 2011 Nov 11


  • Age-related hearing loss (AHL)
  • Cochlea
  • Gentamicin ototoxicity
  • NF-E2-related factor (Nrf2)
  • Reactive oxygen species (ROS)


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