COCHLEAR PROTECTION FROM CARBON-MONOXIDE EXPOSURE BY FREE-RADICAL BLOCKERS IN THE GUINEA-PIG

Acute carbon monoxide exposure produces a significant impairment in hi gh-frequency auditory sensitivity that can be prevented using the N-me thyl-D-aspartate receptor blocker MK-801. This finding suggests an exc itotoxic component to carbon monoxide ototoxicity and establishes the potential for free radical formation. Free radical scavengers and inhi bitors are protective in many organs, including the brain and cochlea, during hypoxic events such as ischemia/reperfusion and, in the cochle a, during noise exposure. This study evaluated the protection afforded by two such agents, phenyl-n-tert-butyl-nitrone (PBN), which acts as a general free radical scavenger, and allopurinol, which acts as a fre e radical inhibitor specific to the xanthine oxidase metabolic pathway . Guinea pigs were pretreated with PBN (100 mg/kg ip), allopurinol (10 0 mg/kg ip), or saline 1 hr prior to exposure to carbon monoxide (35 m l/kg ip) or to an equal volume of air. They were monitored at 15, 30, and 60 min after carbon monoxide exposure for alterations in compound action potential threshold and cochlear microphonic amplitude. The gro ups receiving carbon monoxide alone displayed characteristic compound action potential threshold elevations particularly at the higher test frequencies (16-40 kHz), consistent with earlier studies; no loss of c ochlear microphonic amplitude was exhibited. Both free radical inhibit ors, PBN and allopurinol, blocked loss of auditory threshold sensitivi ty produced by carbon monoxide. These data suggest that free radical g eneration may play a significant role in the impairment of high-freque ncy auditory sensitivity resulting from carbon monoxide. (C) 1997 Acad emic Press.