l-N-acetylcysteine protects outer hair cells against TNFα initiated ototoxicity in vitro

Joshua A. Tillinger, Chhavi Gupta, Kadri Ila, Jamal Ahmed, Jeenu Mittal, Thomas R. Van De Water, Adrien A. Eshraghi

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Objective: The present study is aimed at determining the efficacy and exploring the mechanisms by which l-N-acetylcysteine (l-NAC) provides protection against tumor necrosis factor-alpha (TNFα)-induced oxidative stress damage and hair cell loss in 3-day-old rat organ of Corti (OC) explants. Previous work has demonstrated a high level of oxidative stress in TNFα-challenged OC explants. TNFα can potentially play a significant role in hair cell loss following an insult to the inner ear. l-NAC has shown to provide effective protection against noise-induced hearing loss in laboratory animals but mechanisms of this otoprotective effect are not well-defined. Design: Rat OC explants were exposed to either: (1) saline control (N = 12); (2) TNFα (2 μg/ml, N = 12); (3) TNFα+l-NAC (5 mM, N = 12); (4) TNFα+l-NAC (10 mM, N = 12); or (5) l-NAC (10 mM, N = 12). Outer hair cell (OHC) density, levels of reactive oxygen species (ROS), lipid peroxidation of cell membranes, gluthathione activity, and mitochondrial viability were assayed. Results:l-NAC (5 and 10 mM) provided protection for OHCs from ototoxic level of TNFα in OC explants. Groups treated with TNFα+l-NAC (5 mM) showed a highly significant reduction of both ROS (p < 0.01) and 4-hydroxy-2-nonenal immunostaining (p < 0.001) compared to TNFα-challenged explants. Total glutathione levels were low in TNFα-challenged explants compared to control and TNFα+l-NAC (5 mM) treated explants (p < 0.001). Conclusions:l-NAC is a promising treatment for protecting auditory HCs from TNFα-induced oxidative stress and subsequent loss via programmed cell death.

Original languageEnglish (US)
Pages (from-to)676-684
Number of pages9
JournalActa Oto-Laryngologica
Volume138
Issue number8
DOIs
StatePublished - Aug 3 2018

Keywords

  • TNFα ototoxicity
  • antioxidant
  • l-N-Acetylcysteine

ASJC Scopus subject areas

  • Otorhinolaryngology

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