Abstract |
Acute acoustic trauma (AAT) results in oxidative stress to the cochlea through overproduction of cellular reactive oxygen, nitrogen, and other free radical species appearing from 1 h to 10 days after noise exposure. It has been shown that N-acetyl-L-cysteine (NAC), a glutathione prodrug, and acetyl-L-carnitine ( ALCAR), a mitochondrial biogenesis agent, are effective in reducing noise-induced hearing loss. Phenyl N-tert-butylnitrone (PBN), a nitrone-based free radical trap, appears to suppress oxidative stress in a variety of disorders and several biological models. In this study, we tested whether 4-hydroxy PBN (4-OHPBN), a major metabolite of PBN, administered 4 h after noise exposure is effective in treating noise-induced hearing loss and whether a combination of antioxidant drugs (4-OHPBN plus NAC and 4-OHPBN plus NAC plus ALCAR) provides greater efficacy in attenuating AAT since each agent addresses different injury mechanisms. Chinchilla were exposed to a 105 dB octave-band noise centered at 4 kHz for 6 h. 4-OHPBN and combinations of antioxidant drugs were intraperitoneally administered beginning 4 h after noise exposure. Hearing threshold shifts in auditory brainstem responses and missing outer hair cell counts were obtained. 4-OHPBN reduced threshold shifts in a dose-dependent manner while both drug combinations showed greater effects. These results demonstrate that 4-OHPBN and combinations of antioxidants can effectively treat acute acoustic trauma and drug combinations may increase the effectiveness of treatment and decrease the required individual medication dose.
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Authors | Chul-Hee Choi, Kejian Chen, Angelica Vasquez-Weldon, Ronald L Jackson, Robert A Floyd, Richard D Kopke |
Journal | Free radical biology & medicine
(Free Radic Biol Med)
Vol. 44
Issue 9
Pg. 1772-84
(May 01 2008)
ISSN: 0891-5849 [Print] United States |
PMID | 18328271
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Antioxidants
- Cyclic N-Oxides
- Neuroprotective Agents
- phenyl-N-tert-butylnitrone
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Topics |
- Animals
- Antioxidants
(metabolism)
- Audiometry
- Brain Stem
(embryology)
- Chinchilla
- Cochlea
(injuries, metabolism)
- Cyclic N-Oxides
(pharmacology)
- Female
- Hair Cells, Auditory
(metabolism)
- Hearing Loss
- Hearing Loss, Noise-Induced
- Models, Biological
- Neuroprotective Agents
(pharmacology)
- Noise
- Oxidative Stress
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