title: Effectiveness of 4-hydroxy phenyl N-tert-butylnitrone (4-OHPBN) alone and in combination with other antioxidant drugs in the treatment of acute acoustic trauma in chinchilla.
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.
authors.affiliation: Hough Ear Institute, Oklahoma City, OK 73112, USA. Chul-Hee.Choi@integrisok.com
authors.forename: Chul-Hee
authors.initials: CH
authors.lastname: Choi
authors.forename: Kejian
authors.initials: K
authors.lastname: Chen
authors.forename: Angelica
authors.initials: A
authors.lastname: Vasquez-Weldon
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Jackson
authors.forename: Robert A
authors.initials: RA
authors.lastname: Floyd
authors.forename: Richard D
authors.initials: RD
authors.lastname: Kopke
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001299:Audiometry; D001933:Brain Stem / Q000196:embryology; D002682:Chinchilla; D003051:Cochlea / Q000293:injuries* / Q000378:metabolism*; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D005260:Female; D006198:Hair Cells, Auditory / Q000378:metabolism; D034381:Hearing Loss; D006317:Hearing Loss, Noise-Induced; D008954:Models, Biological; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009622:Noise; D018384:Oxidative Stress
chemical_list: D000975:Antioxidants; D003497:Cyclic N-Oxides; D018696:Neuroprotective Agents; C029217:phenyl-N-tert-butylnitrone