<scp>l</scp>-<i>N</i>-acetylcysteine protects outer hair cells against TNFα initiated ototoxicity <i>in vitro</i>

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

doi:10.1080/00016489.2018.1440086

Cited by 10 publications

(11 citation statements)

References 18 publications

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“…Therefore, how to select the effective antioxidant for SSNHL has become a puzzled problem to be solved. N-acetylcysteine (NAC), as a precursor of glutathione (GSH) and a limiting factor in the process of GSH synthesis, is one of the antioxidants commonly used in the inner ear (Duan et al, 2004;Pathak et al, 2015;Tillinger et al, 2018). It has been clinically proven to be effective as a single therapy in the treatment of SSNHL or cisplatin-induced hearing loss (Riga et al, 2013;Chen and Young, 2016).…”

Section: Introductionmentioning

confidence: 99%

N-Acetylcysteine Combined With Dexamethasone Treatment Improves Sudden Sensorineural Hearing Loss and Attenuates Hair Cell Death Caused by ROS Stress

Bai

Chen

et al. 2021

Front. Cell Dev. Biol.

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Sudden sensorineural hearing loss (SSNHL) is a common emergency in the world. Increasing evidence of imbalance of oxidant–antioxidant were found in SSNHL patients. Steroids combined with antioxidants may be a potential strategy for the treatment of SSNHL. In cochlear explant experiment, we found that N-acetylcysteine (NAC) combined with dexamethasone can effectively protect hair cells from oxidative stress when they were both at ineffective concentrations alone. A clinic trial was designed to explore whether oral NAC combined with intratympanic dexamethasone (ITD) as a salvage treatment has a better therapeutic effect. 41 patients with SSNHL were randomized to two groups. 23 patients in control group received ITD therapy alone, while 18 patient s in NAC group were treated with oral NAC and ITD. The patients were followed-up on day 1st (initiation of treatment) and day 14th. Overall, there was no statistical difference in final pure-tone threshold average (PTA) improvement between those two groups. However, a significant hearing gain at 8,000 Hz was observed in NAC group. Moreover, the hearing recovery rates of NAC group is much higher than that in control group. These results demonstrated that oral NAC in combination with ITD therapy is a more effective therapy for SSNHL than ITD alone.

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Section: Introductionmentioning

confidence: 99%

N-Acetylcysteine Combined With Dexamethasone Treatment Improves Sudden Sensorineural Hearing Loss and Attenuates Hair Cell Death Caused by ROS Stress

Bai

Chen

et al. 2021

Front. Cell Dev. Biol.

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“…16,17 It has been demonstrated that in AGA, androgens lead to an increase in sebum, bacteria colonies, and porphyrins in tissues influenced by disease and that antioxidant treatment affords protection against hair loss associated with TNF-α-related inflammation and oxidative stress. 18,19 It has been reported by various studies that fibrosis is associated with TGF-β1 in AGA and that androgens play a role in the regulation of ROS in dermal papilla cells and suppress hair growth by increasing the secretion of TGF-β1. [20][21][22] It has been proposed that in physiological concentrations, DHT leads to markedly increased NO levels in dermal papilla cells and NO may play a part in the pathogenesis of AA (Alopecia Areata) via the increase in oxidative cell damage.…”

Section: Discussionmentioning

confidence: 99%

Examination of androgenetic alopecia with serum biomarkers

Balık

Balik

Aktaş

et al. 2020

J of Cosmetic Dermatology

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Androgenetic alopecia (AGA) is the most common type of hair loss and affects approximately 50% of the male population. 1,2 Androgens, growth factors (GFs), age, genetic susceptibility, racial factors, and local factors are incriminated in the pathogenesis of AGA, and follicular miniaturization plays the leading role. 3 In the treatment of AGA, limited success has been obtained with hair growth supporters and androgen metabolism modulators, which suggest that other pathogenic pathways may be considered. 4 Dihydrotestosterone (DHT) is considered the main culprit in AGA.However, it is thought that androgen derived from dermal papilla cells affects other components regulating the growth of hair follicles. 4 In order to evaluate oxidative stress, microinflammation and perifollicular fibrosis processes thought to play a part in the pathogenesis of AGA, serum samples were drawn from patient and control groups, and NFκ-B, TNF-α, TGF-β1, thioredoxin, nitric oxide (NO), TAS, TOS levels, and serum thiol disulfide homeostasis (native thiol, total thiol, disulfide) were measured and compared.To our knowledge, the present study is the first study carried out

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“…[17,27,28]. In addition to its direct antioxidant effect, L-NAC provides protection for hair cells against TNF-α induced toxicity in OC explants [29]. Furthermore, L-NAC reduces ROS/RNS-induced glutamate excitotoxicity in spiral ganglion cell lines and can protect against both the intrinsic and extrinsic apoptotic pathways following chemical insult in hair cells and auditory nerves.…”

Section: Discussionmentioning

confidence: 99%

Evaluating the Efficacy of L-N-acetylcysteine and Dexamethasone in Combination to Provide Otoprotection for Electrode Insertion Trauma

Eshraghi

Shahal

Davies

et al. 2020

JCM

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Background: Electrode insertion trauma (EIT) during cochlear implantation (CI) can cause loss of residual hearing. L-N-acetylcysteine (L-NAC) and dexamethasone (Dex) have been individually shown to provide otoprotection albeit at higher concentrations that may be associated with adverse effects. Objective/Aims: The aim of this study is to determine whether L-NAC and Dex could be combined to decrease their effective dosage. Materials and Methods: The organ of Corti (OC) explants were divided into various groups: 1) control; 2) EIT; 3) EIT treated with different concentrations of Dex; 4) EIT treated with different concentrations of L-NAC; 5) EIT treated with L-NAC and Dex in combination. Hair cell (HC) density, levels of oxidative stress, proinflammatory cytokines and nitric oxide (NO) was determined. Results: There was a significant loss of HCs in explants subjected to EIT compared to the control group. L-NAC and Dex in combination was able to provide significant otoprotection at lower concentrations compared to individual drugs. Conclusions and Significance: A combination containing L-NAC and Dex is effective in protecting sensory cells at lower protective doses than each compound separately. These compounds can be combined allowing a decrease of potential side effects of each compound and providing significant otoprotection for EIT.

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

Abstract: l-NAC is a promising treatment for protecting auditory HCs from TNFα-induced oxidative stress and subsequent loss via programmed cell death.

Cited by 10 publications

References 18 publications

N-Acetylcysteine Combined With Dexamethasone Treatment Improves Sudden Sensorineural Hearing Loss and Attenuates Hair Cell Death Caused by ROS Stress

N-Acetylcysteine Combined With Dexamethasone Treatment Improves Sudden Sensorineural Hearing Loss and Attenuates Hair Cell Death Caused by ROS Stress

Examination of androgenetic alopecia with serum biomarkers

Evaluating the Efficacy of L-N-acetylcysteine and Dexamethasone in Combination to Provide Otoprotection for Electrode Insertion Trauma

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