Dose and time-dependent protection of the antioxidant N-l-acetylcysteine against impulse noise trauma

Duan, Maoli; Qiu, Jianxin; Laurell, Göran; Olofsson, Åke; Counter, S. Allen; Borg, Erik

doi:10.1016/j.heares.2004.02.005

Cited by 97 publications

(66 citation statements)

References 33 publications

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“…The results of this study did not demonstrated any significant differences in the temporary threshold shift that resulted from the nightclub noise exposure between NAC treatment and the placebo groups; however, this study did not evaluate these 2 groups for PTS [65]. The result of this is consistent with the results obtained from many animal studies that have found the otoprotective effects of NAC evident primarily on PTS, but not on temporary threshold shift [66,67,68]. In another prospective randomized double-blind placebo-controlled trial, 566 military subjects were tested for auditory threshold shifts, DPOAEs, and tinnitus before and after noise exposure that resulted from 2 weeks of routine military weapons training.…”

Section: Antioxidantssupporting

confidence: 82%

Blocking Pro-Cell-Death Signal Pathways to Conserve Hearing

Dinh

Water²

2009

Audiol Neurotol

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The programmed cell death of stress-damaged auditory hair cells can occur through a variety of signal pathways, and therapeutic modalities that block pro-cell-death pathways are being developed and evaluated for hearing preservation. Because of their ability to have both anti-inflammatory and anti-apoptotic actions, corticosteroids have long been used to protect against several types of acute sensorineural hearing loss. Other anti-apoptotic drugs that target the mitogen-activated protein kinase (MAPK)/c-Jun-N terminal kinase (JNK) signal cascade, such as D-JNKI-1 (AM-111) and SP600125, have produced promising results both in vitro and in laboratory animal studies, with AM-111 showing promise in preliminary clinical trials. Antioxidant drugs, e.g. sodium thiosulfate, N-acetylcysteine, and D-methionine, have been shown in animal studies to attenuate permanent threshold shifts in hearing by reducing oxidative stress. In addition to reviewing selected therapeutic trends for the conservation of hearing, we review our experiences with dexamethasone and D-JNKI-1 and report results from our current research.

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Section: Antioxidantssupporting

confidence: 82%

Blocking Pro-Cell-Death Signal Pathways to Conserve Hearing

Dinh

Water²

2009

Audiol Neurotol

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“…Nacetylcysteine (NAC), a glutathione precursor and ROS scavenger, has been effective in reducing PTS in noise-exposed guinea pigs (Ohinata et al, 2003;Duan et al, 2004) and chinchillas (delivered in combination with salicylate, see Kopke et al, 2000), with no effect on TTS in man (Kramer et al, 2006) or rodents (Kopke et al, 2000;Duan et al, 2004). Given that a major determinant of GSH level is bioavailable cysteine, and that cysteine can be derived from methionine, an alternative strategy has been pre-treatment with D-methionine.…”

Section: Endogenous Antioxidant Defense Against Nihlmentioning

confidence: 99%

Mechanisms of noise-induced hearing loss indicate multiple methods of prevention

et al. 2007

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Recent research has shown the essential role of reduced blood flow and free radical formation in the cochlea in noise-induced hearing loss (NIHL). The amount, distribution, and time course of free radical formation have been defined, including a clinically significant late formation 7-10 days following noise exposure, and one mechanism underlying noise-induced reduction in cochlear blood flow has finally been identified. These new insights have led to the formulation of new hypotheses regarding the molecular mechanisms of NIHL; and, from these, we have identified interventions that prevent NIHL, even with treatment onset delayed up to 3 days post-noise. It is essential to now assess the additive effects of agents intervening at different points in the cell death pathway to optimize treatment efficacy. Finding safe and effective interventions that attenuate NIHL will provide a compelling scientific rationale to justify human trials to eliminate this single major cause of acquired hearing loss.

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“…Upregulation of the endogenous antioxidant glutathione reduces NIHL and cell pathology [44,45], whereas the opposite is observed with reduced endogenous antioxidants [20,22,23,44]. That exogenous antioxidant agents reduce sensory cell death and NIHL has been well demonstrated in animal studies using a variety of free radical scavengers [24,[44][45][46][47][48][49][50][51][52][53][54][55][56], including several studies with dietary antioxidants [50,[57][58][59][60]. Magnesium supplements also reduce NIHL [61][62][63][64][65][66][67][68][69].…”

mentioning

confidence: 99%

Free radical scavengers vitamins A, C, and E plus magnesium reduce noise trauma

Prell

Hughes

Miller

2007

Free Radical Biology and Medicine

201

188

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Free radical formation in the cochlea plays a key role in the development of noise-induced hearing loss (NIHL). The amount, distribution, and time course of free radical formation have been defined, including a clinically significant formation of both reactive oxygen species and reactive nitrogen species 7-10 days following noise exposure. Reduction in cochlear blood flow as a result of free radical formation has also been described. Here we report that the antioxidant agents, vitamins A, C, and E, act in synergy with magnesium to effectively prevent noise-induced trauma. Neither the antioxidant agents nor magnesium reliably reduced NIHL or sensory cell death with the doses we used when these agents were delivered alone. In combination, however, they were highly effective in reducing both hearing loss and cell death even with treatment initiated just one hour prior to noise exposure. This study supports roles for both free radical formation and noise-induced vasoconstriction in the onset and progression of NIHL. Identification of this safe and effective antioxidant intervention that attenuates NIHL provides a compelling rationale for human trials in which free radical scavengers are used to eliminate this single major cause of acquired hearing loss. Keywords cochlea; free radical; noise; hearing; antioxidant; vasodilation Mechanical destruction of cells in the organ of Corti was once assumed to be the primary cause of noise-induced hearing loss (NIHL) [1][2][3][4][5][6][7][8], with perhaps some effect of reduced blood flow to the inner ear [9][10][11][12][13][14][15][16][17][18]. We now know that another key factor is intense metabolic activity that results in production of excess free radicals [19][20][21][22][23] and lipid peroxidation products [24]. Noise-induced production of reactive oxygen species (ROS) in the cochlea has now been well characterized, and several recent reviews are available [25][26][27]. Mitochodrial dysfunction and ROS production have been implicated in numerous neurodegenerative syndromes and diseases [28-34, see 35,36]. The use of antioxidant agents holds significant therapeutic promise for many neurodegenerative processes [32,33,[37][38][39][40][41][42], and there is some suggestion that Correspondence to: C. G. Le Prell, Kresge Hearing Research Institute, University of Michigan, 1301 East Ann Street, Ann Arbor, MI 48109-0506, USA. Tel: +1-734-763-5104; fax +1-734-764-0014. E-mail address: colleeng@umich.edu. Disclosure. Dr. Miller is a founding member and Chairman of the Board of Directors at OtoMedicine, Inc., a company that has an option to license the intellectual property described in this report. Dr. Le Prell is a paid consultant to OtoMedicine, Inc. Drs. Miller and Le Prell have disclosed these relationships to the Medical School Conflict of Interest Board at the University of Michigan; conflict management plans including semi-annual review by the Board are in place.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publicatio...

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Dose and time-dependent protection of the antioxidant N-l-acetylcysteine against impulse noise trauma

Cited by 97 publications

References 33 publications

Blocking Pro-Cell-Death Signal Pathways to Conserve Hearing

Blocking Pro-Cell-Death Signal Pathways to Conserve Hearing

Mechanisms of noise-induced hearing loss indicate multiple methods of prevention

Free radical scavengers vitamins A, C, and E plus magnesium reduce noise trauma

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