Ebselen treatment reduces noise induced hearing loss via the mimicry and induction of glutathione peroxidase

Kil, Jonathan; Pierce, Carol; Tran, Huy; Gu, Rende; Lynch, Eric D.

doi:10.1016/j.heares.2006.08.006

Cited by 127 publications

(87 citation statements)

References 29 publications

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“…GSH-Px activities decreased in the rat brain after 30 d noise exposure (8). Noise induced hearing loss involves a decrease in GSH-Px activity and a subsequent loss of outer hair cells (25). The significantly decreased CAT and GSH-Px activities were observed in the rat brain after 30 days of noise exposure (8).…”

Section: Discussionmentioning

confidence: 93%

Noise Induces Oxidative Stress in Rat

et al. 2009

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Section: Discussionmentioning

confidence: 93%

Noise Induces Oxidative Stress in Rat

et al. 2009

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“…Ebselen is a potent glutathione peroxidase (GPx) mimic; GPx catalyzes the anti-oxidant actions of GSH [107]. Pretreatment with ebselen reduces NIHL [108][109][110][111].…”

Section: Alternative Strategiesmentioning

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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“…D-methionine would be another logical choice (Rewerska et al, 2013). Ebselen represents another potential choice for a therapeutic agent (Kil et al, 2007); however, the human clinical exposure to ebselen is significantly less than for NAC.…”

Section: Introductionmentioning

confidence: 99%