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) i s known to result in more severe permanent threshold shifts than exposure t o noise alone. We have previously demonstrated that such potentiation of no ise-induced auditory impairment by CO can be prevented by the administratio n of a nitrone spin-trapping agent. Although such protection implicates inj ury via free radical pathways, drug-induced protection does not provide dir ect evidence for the presence of free radicals in the cochlea. The objectiv e of this study was to demonstrate the actual presence of nitrone spin addu cts in the cochlea following simultaneous exposure to noise and CO. Using e lectrophysiological end-points. the protective effects of the nitrone spin- trapping agent alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN) were as sessed 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 d one by electron paramagnetic resonance spectroscopy (EPR). The noise used w as octave band noise with center frequency 13.6 kHz at 100 dB(Lin) for a du ration of 2 h. The level of CO used was 1200 ppm. Electro physiological res ults demonstrate that POBN protects against combined exposure to noise plus CO. The EPR study demonstrates POBN spin adducts in the cochleae of animal s exposed to noise plus CO. Therefore, this study provides evidence to the hypothesis that ototoxicity due to noise plus CO exposure is mediated via f ree radicals. (C) 2001 Elsevier Science B.V. All rights reserved.