Direct inner ear infusion of dexamethasone attenuates noise-induced trauma in guinea pig

Takemura, Keiji; Komeda, Mototane; Yagi, Minoru; Himeno, Chiemi; Izumikawa, Masahiko; Doi, Tadashi; Kuriyama, Hiromichi; Miller, Josef M.; Yamashita, Toshio

doi:10.1016/j.heares.2004.06.003

Cited by 165 publications

(120 citation statements)

References 84 publications

(87 reference statements)

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“…Intra-cochlear infusion of dexamethasone, a member of the glucocorticoid family of steroids, protects hair cell survival and auditory function from toxic effects of noise (Lamm and Arnold, 1998;Takemura et al, 2004), and other insults (Himeno et al, 2002;Tabuchi et al, 2003). Consistent with the notion of endogenous steroid-based protection in the inner ear, noise elevates glucocorticoid plasma concentration , and down-regulates glucocorticoid receptors in the cochlea (Terunuma et al, 2001).…”

Section: Growth Factorsmentioning

confidence: 79%

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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Section: Growth Factorsmentioning

confidence: 79%

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

et al. 2007

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“…Free radical formation has been implicated in all. Interventions can be directed at preventing initial ROS formation and maintaining cochlear blood flow (as reported here and by others); alternative therapeutic interventions and strategies include neurotrophic growth factors [119][120][121][122], steroids [123,124], calcineurin inhibitors [125,126], caspase inhibitors [127][128][129][130][131][132], and Src protein tyrosine kinase (Src-PTK) inhibitors [133]. Each of these are at least partially effective in prevention of hearing loss and hair cell death; none of these strategies have alone been sufficiently effective.…”

Section: Discussionmentioning

confidence: 94%

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

Prell

Hughes

Miller

2007

Free Radical Biology and Medicine

198

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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“…In an attempt to better control the drug level at the RWM, continuous drug application has been employed, via partially or fully implantable catheter systems and pumps. In animals, the mini-osmotic ALZET-pump (DURECT ™ , Co., Cupertino, USA) has been widely used both for drug delivery to the middle ear (85) and for intracochlear delivery of drugs (29,36,86).…”

Section: Ii) Continuous or Discontinuous Drug Application Via Partly mentioning

confidence: 99%

“…There is also interest in the use of growth factors, antioxidants, apoptosis inhibitors and antisense-oligonucleotides. Animal experiments have shown promising results using locally applied drugs to provide otoprotection from noise and drug toxicity (28,29,30,31,32,33,34,35,36). One extension of such studies is local viral and non-viral gene transfer for the sustained treatment of inner ear disorders (37,38,38,40,41,42).…”

Section: Introductionmentioning

confidence: 99%

Local inner-ear drug delivery and pharmacokinetics

Salt

Plontke

2005

Drug Discovery Today

155

123

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SummaryA number of drugs are in widespread clinical use for the treatment of inner ear disorders by applying them directly to the inner ear. Many new substances and drug delivery systems specific to the inner ear are under development, and in some cases are undergoing evaluations in animal experiments and in clinical studies. The pharmacokinetics of drugs in the inner ear, however, is not well defined and the field is plagued by technical problems in obtaining pure samples of the inner ear fluids for analysis. Nevertheless, a basic understanding of the mechanisms of drug dispersal in the inner ear has emerged that facilitates the design and interpretation of future pharmacokinetic studies.

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Direct inner ear infusion of dexamethasone attenuates noise-induced trauma in guinea pig

Cited by 165 publications

References 84 publications

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

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

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

Local inner-ear drug delivery and pharmacokinetics

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