Evaluating the Efficacy of Taurodeoxycholic Acid in Providing Otoprotection Using an in vitro Model of Electrode Insertion Trauma

Viraj Shah, Rahul Mittal, David Shahal, Priyanka Sinha, Erdogan Bulut, Jeenu Mittal, Adrien A. Eshraghi

Research output: Contribution to journalArticlepeer-review

Abstract

Cochlear implants (CIs) are widely used to provide auditory rehabilitation to individuals having severe to profound sensorineural hearing loss (SNHL). However, insertion of electrode leads to inner trauma and activation of inflammatory and apoptotic signaling cascades resulting in loss of residual hearing in implanted individuals. Pharmaceutical interventions that can target these signaling cascades hold great potential for preserving residual hearing by preventing sensory cell damage. Bile salts have shown efficacy in various regions of the body as powerful antioxidants and anti-inflammatory agents. However, their efficacy against inner ear trauma has never been explored. The objective of this study was to determine whether taurodeoxycholic acid (TDCA), a bile salt derivative, can prevent sensory cell damage employing an in vitro model of electrode insertion trauma (EIT). The organ of Corti (OC) explants were dissected from postnatal day 3 (P-3) rats and placed in serum-free media. Explants were divided into control and experimental groups: (1) untreated controls; (2) EIT; (3) EIT+ TDCA (different concentrations). Hair cell (HC) density, analyses of apoptosis pathway (cleaved caspase 3), levels of reactive oxygen species (ROS) as well as inducible nitric oxide synthase (iNOS) activity and Mitochondrial Membrane Potential (MMP) were assayed. Treatment with TDCA provided significant otoprotection against HC loss in a dose-dependent manner. The molecular mechanisms underlying otoprotection involved decreasing oxidative stress, lowering levels of iNOS, and abrogating generation of cleaved caspase 3. The results of the present study suggest that TDCA provides efficient otoprotection against EIT, in vitro and should be explored for developing pharmaceutical interventions to preserve residual hearing post-cochlear implantation.

Original languageEnglish (US)
Article number113
JournalFrontiers in Molecular Neuroscience
Volume13
DOIs
StatePublished - Jul 14 2020

Keywords

  • caspase-3 pathway
  • cochlear implant
  • electrode insertion trauma
  • nitric oxide
  • oxidative stress
  • taurodeoxycholic acid

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Evaluating the Efficacy of Taurodeoxycholic Acid in Providing Otoprotection Using an in vitro Model of Electrode Insertion Trauma'. Together they form a unique fingerprint.

Cite this