Free radical generation in the cochlea during combined exposure to noise and carbon monoxide: an electrophysiological and an EPR study

Ototoxicity following combined exposure to noise and carbon monoxide (CO) is known to result in more severe permanent threshold shifts than exposure to noise alone. We have previously demonstrated that such potentiation of noise-induced auditory impairment by CO can be prevented by the administration of a nitrone spin-trapping agent. Although such protection implicates injury via free radical pathways, drug-induced protection does not provide direct evidence for the presence of free radicals in the cochlea. The objective of this study was to demonstrate the actual presence of nitrone spin adducts in the cochlea following simultaneous exposure to noise and CO. Using electrophysiological end-points. the protective effects of the nitrone spin-trapping agent alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN) were assessed following combined exposure of adult male Long Evans hooded rats to noise and CO. In addition, an ex-vivo evaluation of POBN spin adducts was done by electron paramagnetic resonance spectroscopy (EPR). The noise used was octave band noise with center frequency 13.6 kHz at 100 dB(Lin) for a duration of 2 h. The level of CO used was 1200 ppm. Electro physiological results demonstrate that POBN protects against combined exposure to noise plus CO. The EPR study demonstrates POBN spin adducts in the cochleae of animals exposed to noise plus CO. Therefore, this study provides evidence to the hypothesis that ototoxicity due to noise plus CO exposure is mediated via free radicals. (C) 2001 Elsevier Science B.V. All rights reserved.