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Mechanisms of oxidative stress in the potentiation of noise-induced hearing loss by acrylonitrile.

Authors
Pouyatos-B; Fechterr-L
Source
Abstr 29th Midwinter Res Meet 2006 Feb; 29:11-12
NIOSHTIC No.
20041688
Abstract
Acrylonitrile (ACN), one of the top 50 chemicals produced in the world, is a very powerful pro-oxidant compound whose metabolism leads to a profound glutathione (GSH) depletion and to a production of cyanide (CN) which, in turn, can inhibit superoxide dismutase (SOD). ACN, by itself, is not ototoxic, but we have shown that it can strongly promote noise-induced hearing loss (NIHL), even at noise levels that do not produce auditory impairment. The mechanism by which ACN renders the cochlea more vulnerable to noise damage is still unknown, but we hypothesize that the decrease of GSH and/or the inhibition of SOD reduce the cochlear intrinsic anti-oxidant defenses and ultimately create oxidative stress. In this study, we investigated in adult Long-Evans rats the effect of the alteration of CN production through the ACN metabolism on the promotion of NIHL by ACN. For this purpose, two different drugs were used: (1) Sodium thiosulfate (STS), a CN antidote commonly used in humans in case of CN poisoning and (2) 4-methylpyrazole (4MP) which blocks ACN metabolism through the oxidative pathway, preventing CN formation. We observed that, while both STS and 4MP drastically reduced CN production by more than 80%, they did not protect against the potentiating effect of ACN. This result suggests that CN is not implicated in the potentiation of NIHL by ACN. Further studies are proposed to determine the role of GSH depletion in the increase of vulnerability to noise induced by ACN.
Keywords
Noise-exposure; Exposure-levels; Noise-induced-hearing-loss; Noise-exposure; Noise; Hearing; Hearing-disorders; Hearing-loss; Laboratory-animals; Animals; Cell-damage; Cellular-reactions; Author Keywords: cochlea; noise; oxidative stress; acrylonitrile; superoxide dismutase; glutathione; cyanide
CAS No.
107-13-1
Publication Date
20060205
Document Type
Abstract
Editors
Santi-PA
Funding Type
Grant
Fiscal Year
2006
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-003973; Grant-Number-R01-OH-003481
ISSN
0742-3152
Source Name
Abstracts of the 29th Midwinter Research Meeting
State
MD; NJ; MO
Performing Organization
Washington University
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