N-acetylcysteine Prevents Gentamicin Ototoxicity in a Rat Model

Somdas, Mehmet Akıf; Korkmaz, Ferhat; Gürgen, Seren Gülşen; Sağıt, Mustafa; Akçadağ, Alper

doi:10.5152/iao.2015.650

Cited by 24 publications

(21 citation statements)

References 24 publications

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“…Several anti-oxidants like N -acetylcysteine, D-methionine and edaravone reduce aminoglycoside-induced ototoxicity in preclinical models (Somdaş et al, 2015 ; Campbell et al, 2016 ; Turan et al, 2017 ), suggesting that drug-induced generation of reactive oxygen species leads to aminoglycoside-induced ototoxicity. Several anti-oxidants show otoprotection against both aminoglycosides and cisplatin, implying that induction of oxidative stress is a shared mechanism of cytotoxicity for these ototoxins (Lorito et al, 2011 ; Tate et al, 2017 ).…”

Section: Potential Clinical Approaches To Reduce Aminoglycoside Uptakmentioning

confidence: 99%

Aminoglycoside-Induced Cochleotoxicity: A Review

Jiang

Karasawa

Steyger

2017

Front. Cell. Neurosci.

215

165

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Aminoglycoside antibiotics are used as prophylaxis, or urgent treatment, for many life-threatening bacterial infections, including tuberculosis, sepsis, respiratory infections in cystic fibrosis, complex urinary tract infections and endocarditis. Although aminoglycosides are clinically-essential antibiotics, the mechanisms underlying their selective toxicity to the kidney and inner ear continue to be unraveled despite more than 70 years of investigation. The following mechanisms each contribute to aminoglycoside-induced toxicity after systemic administration: (1) drug trafficking across endothelial and epithelial barrier layers; (2) sensory cell uptake of these drugs; and (3) disruption of intracellular physiological pathways. Specific factors can increase the risk of drug-induced toxicity, including sustained exposure to higher levels of ambient sound, and selected therapeutic agents such as loop diuretics and glycopeptides. Serious bacterial infections (requiring life-saving aminoglycoside treatment) induce systemic inflammatory responses that also potentiate the degree of ototoxicity and permanent hearing loss. We discuss prospective clinical strategies to protect auditory and vestibular function from aminoglycoside ototoxicity, including reduced cochlear or sensory cell uptake of aminoglycosides, and otoprotection by ameliorating intracellular cytotoxicity.

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Section: Potential Clinical Approaches To Reduce Aminoglycoside Uptakmentioning

confidence: 99%

Aminoglycoside-Induced Cochleotoxicity: A Review

Jiang

Karasawa

Steyger

2017

Front. Cell. Neurosci.

215

165

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“…However, it has been reported to exert ototoxic side effects leading to cochlear and/or vestibular damage [8]. Mechanistically, the ototoxic effects of gentamicin are mediated by the oxidative stress pathway [9,10], apoptosis [11][12][13], autophagy [14,15], and the Akt survival pathway [16][17][18]. Apoptosis plays an important role in maintaining intracellular homeostasis and participates in the pathogenesis of hearing loss [19].…”

Section: Introductionmentioning

confidence: 99%

Otoprotective Effect of 2,3,4′,5-Tetrahydroxystilbene-2-O-β-d-Glucoside on Gentamicin-Induced Apoptosis in Mouse Cochlear UB/OC-2 Cells

Wen

Lin²,

et al. 2020

Molecules

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Excessive levels of reactive oxygen species (ROS) lead to mitochondrial damage and apoptotic cell death in gentamicin-induced ototoxicity. 2,3,4’,5-Tetrahydroxystilbene-2-O-β-d-glucoside (THSG), a bioactive constituent, isolated from Polygonum multiflorum Thunb., exhibits numerous biological benefits in treating aging-related diseases by suppressing oxidative damage. However, its protective effect on gentamicin-induced ototoxicity remains unexplored. Therefore, here, we aimed to investigate the otoprotective effect of THSG on gentamicin-induced apoptosis in mouse cochlear UB/OC-2 cells. We evaluated the effect of gentamicin and THSG on the ROS level, superoxide dismutase (SOD) activity, mitochondrial membrane potential, nuclear condensation, and lactate dehydrogenase (LDH) release, and the expression of apoptosis-related proteins was assessed to understand the molecular mechanisms underlying its preventive effects. The findings demonstrated that gentamicin increased ROS generation, LDH release, and promoted apoptotic cell death in UB/OC-2 cells. However, THSG treatment reversed these effects by suppressing ROS production and downregulating the mitochondrial-dependent apoptotic pathway. Additionally, it increased the SOD activity, decreased the expression of apoptosis-related proteins, alleviated the levels of the apoptotic cells, and impaired cytotoxicity. To the best of our knowledge, this is the first study to demonstrate that THSG could be a potential therapeutic option to attenuate gentamicin-induced ototoxicity.

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“…A decrease in OAE produced by outer hair cells provides evidence of ototoxicity, which has been previously studied (5,7,17).…”

Section: Discussionmentioning

confidence: 97%

“…N-acetylcysteine (NAC), previously shown to decrease ototoxicity caused by different agents, is known to be a powerful in vitro antioxidant (16)(17)(18). The current study aimed to determine the effect of NAC on the reduction of cisplatin ototoxicity.…”

Section: Introductionmentioning

confidence: 99%

N-Acetyl Cysteine Reduces Cisplatin Ototoxicity

Somdas¹,

Güntürk²,

Avcı³

et al. 2016

Erciyes Med J

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Objective: To investigate the changes in otoacoustic emissions (OAEs) for detecting the ototoxicity of cisplatin and to study the possible preventive effect of N-acetylcysteine (NAC) in cisplatin ototoxicity. Materials and Methods:This study was conducted on 21 Wistar albino rats in four groups. Cisplatin, cisplatin plus NAC, NAC alone, and saline were intraperitoneally administered. The rats were anesthetized to study the otoacoustic emissions before and after the experiment.Results: The OAEs were attenuated in the cisplatin group: (−1.31/−4.90), (6.28/4.58), (4.00/0.93), (2.73/−3.74), (2.66/−4.53).The group that received NAC in addition to cisplatin had better OAEs.Conclusion: Cisplatin ototoxicity can be detected by OAE testing in rats, and NAC may reduce the ototoxic effect.

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N-acetylcysteine Prevents Gentamicin Ototoxicity in a Rat Model

Cited by 24 publications

References 24 publications

Aminoglycoside-Induced Cochleotoxicity: A Review

Aminoglycoside-Induced Cochleotoxicity: A Review

Otoprotective Effect of 2,3,4′,5-Tetrahydroxystilbene-2-O-β-d-Glucoside on Gentamicin-Induced Apoptosis in Mouse Cochlear UB/OC-2 Cells

N-Acetyl Cysteine Reduces Cisplatin Ototoxicity

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