MK-801 protects against carbon monoxide-induced hearing loss.
MK-801, a glutamate receptor blocker, has been reported to protect against hypoxic-ischemic neuronal degeneration. The purpose of this study was to investigate the protective effects of MK-801 on cochlear impairment induced by carbon monoxide (CO) in the guinea pig and whether the protection reflected systemic or local effects. Glutamate has been proposed to be the neurotransmitter at the inner hair cell/type I spiral ganglion cell synapse. CO (35 ml/kg ip) elevated the compound action potential threshold at high frequencies (16-40 kHz) 30 min after treatment. In the group pretreated with 1 mg/kg MK-801 ip there was no significant elevation of compound action potential threshold 30 min after CO exposure, suggesting that MK-801 provided some protection at this dosage. In the group pretreated with 0.1 mg/kg MK-801 there was protection against cochlear dysfunction 15 min after CO injection, but significant elevation of compound action potential threshold occurred 30 and 60 min after CO exposure. Data also indicated that 1 mM MK-801 applied topically on the round window membrane provided protective effects against CO hypoxia from 15 up to 60 min. This experiment suggests that cochlear impairment induced by CO hypoxia may result from excess extracellular concentrations of glutamate.
Liu
Y
Y
Toxicology Program, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City 73190.
Fechter
L D
LD
D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects; D002248:Carbon Monoxide / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D006168:Guinea Pigs; D034381:Hearing Loss / Q000139:chemically induced* / Q000517:prevention & control*; D008297:Male; D013997:Time Factors
D016291:Dizocilpine Maleate; D002248:Carbon Monoxide