L-N-acetylcysteine protects outer hair cells against TNFα initiated ototoxicity in vitro. (3rd August 2018)

• Record Type: Journal Article
• Authors: Tillinger, Joshua A.; Gupta, Chhavi; Ila, Kadri; Ahmed, Jamal; Mittal, Jeenu; Van De Water, Thomas R.; Eshraghi, Adrien A.
• Is Part Of: Acta oto-laryngologica. Volume 138:Number 8(2018)
• Page Start: 676
• Page End: 684
• Publication Date: 2018-08-03
• Subjects: l-N-Acetylcysteine -- antioxidant -- TNFα ototoxicity; Otolaryngology -- Periodicals; Ear -- Diseases -- Periodicals; Throat -- Diseases -- Periodicals; Otolaryngology -- Electronic Resources; Otorhinolaryngologic Diseases; 617.8
• DOI: 10.1080/00016489.2018.1440086
• Languages: English
• ISSNs: 0001-6489

Abstract

Abstract: Objective: The present study is aimed at determining the efficacy and exploring the mechanisms by whichl - 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.