Protective effects of phenyl-N-tert-butylnitrone on the potentiation of noise-induced hearing loss by carbon monoxide

Free radical injury has been implicated in cochlear damage resulting from exposure to high-intensity noise and due to carbon monoxide (CO) hypoxia. Although exposure to noise plus CO is common in occupational settings and noise-induced hearing loss (NIHL) is enhanced in the presence of CO, potential mechanisms resulting in auditory impairment have not been studied. This study evaluates protective effects of the free radical scavenger phenyl-N-tert-butylnitrone (PBN) against potentiation of NIHL by CO. Three PBN administration protocols have been evaluated in subjects exposed to noise plus CO or noise alone. Long Evans hooded rats were exposed to octave band noise at 100 dB(Lin), center frequency (cf) = 13.6 kHz for a duration of 2 h. The level of CO used was 1200 ppm. Endpoints used to detect permanent auditory impairment were compound action potential (CAP) threshold and 1 mu V root mean square (RMS) cochlear microphonic (CM). Testing was done 4 weeks following exposure. PBN administration prior to and following simultaneous exposure provided significant protection against auditory impairment in subjects receiving noise plus CO. Partial protection was observed in the protocols where PBN was injected following noise plus CO exposure. PBN administration appeared to reduce auditory impairment in animals exposed to noise alone, but the difference was not found to be statistically significant. Protective effects of PBN following simultaneous exposure to noise plus CO suggest that free radicals may be generated during combined exposure. (C) 2000 Academic Press.