Cochlear protection from carbon monoxide exposure by free radical blockers in the guinea pig.
Acute carbon monoxide exposure produces a significant impairment in high-frequency auditory sensitivity that can be prevented using the N-methyl-D-aspartate receptor blocker MK-801. This finding suggests an excitotoxic component to carbon monoxide ototoxicity and establishes the potential for free radical formation. Free radical scavengers and inhibitors are protective in many organs, including the brain and cochlea, during hypoxic events such as ischemia/reperfusion and, in the cochlea, 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 free radical inhibitor specific to the xanthine oxidase metabolic pathway. Guinea pigs were pretreated with PBN (100 mg/kg i.p.), allopurinol (100 mg/kg i.p.), or saline 1 hr prior to exposure to carbon monoxide (35 ml/kg i.p.) 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 groups 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 cochlear microphonic amplitude was exhibited. Both free radical inhibitors, PBN and allopurinol, blocked loss of auditory threshold sensitivity produced by carbon monoxide. These data suggest that free radical generation may play a significant role in the impairment of high-frequency auditory sensitivity resulting from carbon monoxide.
Fechter
L D
LD
Toxicology Program, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City 73190, USA.
Liu
Y
Y
Pearce
T A
TA
D000493:Allopurinol / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D002249:Carbon Monoxide Poisoning / Q000517:prevention & control*; D015687:Cell Hypoxia; D003051:Cochlea / Q000187:drug effects*; D003055:Cochlear Microphonic Potentials / Q000187:drug effects; D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use*; D005609:Free Radicals; D006168:Guinea Pigs; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D009589:Nitrogen Oxides / Q000494:pharmacology / Q000627:therapeutic use*; D018384:Oxidative Stress; D014969:Xanthine Oxidase / Q000378:metabolism
D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D005609:Free Radicals; D018696:Neuroprotective Agents; D009589:Nitrogen Oxides; C029217:phenyl-N-tert-butylnitrone; D000493:Allopurinol; D014969:Xanthine Oxidase