miR-182 prevented ototoxic deafness induced by co-administration of kanamycin and furosemide in rats

Neurosci Lett. 2020 Apr 1:723:134861. doi: 10.1016/j.neulet.2020.134861. Epub 2020 Feb 24.

Abstract

Ototoxic drugs may induce auditory sensory hair cell loss and permanent deafness; however, there is still no effective treatments or prevention strategies for this side effect. A recent study found that microRNA182 (miR-182) protected cochlear hair cells from ototoxic drug-induced apoptosis in vitro. However, it remains unclear whether miR-182 can protect drug-induced deafness in vivo. In this study, we overexpressed cochlear miR-182 in Sprague-Dawley rats by trans-round window niche delivery of miR-182 mimics. The rats subsequently received intraperitoneal injections of kanamycin and furosemide to induce acute cochlear outer hair cell death and permanent deafness. Auditory brainstem response tests showed that miR-182 attenuated permanent threshold shifts. Consistent with this result, miR-182 reduced the loss of outer hair cells and missing stereocilia. miR-182 treatment also increased the level of phosphoinositide-3 kinase regulatory subunit p85α in the outer hair cells after co-administration of kanamycin and furosemide. Our findings suggest that miR-182 has powerful protective potential against ototoxic drug-induced acute auditory sensory hair cell loss and permanent deafness.

Keywords: Hair cell; Hearing loss; Ototoxic drug; Therapeutic; miR-182; microRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / toxicity
  • Deafness / chemically induced
  • Deafness / metabolism*
  • Deafness / prevention & control
  • Drug Combinations
  • Female
  • Furosemide / administration & dosage
  • Furosemide / toxicity*
  • Kanamycin / administration & dosage
  • Kanamycin / toxicity*
  • MicroRNAs / biosynthesis*
  • Ototoxicity / metabolism*
  • Ototoxicity / prevention & control
  • Rats
  • Rats, Sprague-Dawley
  • Sodium Potassium Chloride Symporter Inhibitors / administration & dosage
  • Sodium Potassium Chloride Symporter Inhibitors / toxicity

Substances

  • Anti-Bacterial Agents
  • Drug Combinations
  • MIRN182 microRNA, rat
  • MicroRNAs
  • Sodium Potassium Chloride Symporter Inhibitors
  • Kanamycin
  • Furosemide