Characterization of hydroxyl radical generation in the striatum of free-moving rats due to carbon monoxide poisoning, as determined by in vivo microdialysis.
Carbon monoxide (CO) poisoning caused by CO exposure at 3000 ppm for 40 min resulted in stimulation of hydroxyl radical (*OH) generation (estimated by measuring 2,3-dihydroxybenzoic acid (2,3-DHBA) production from salicylic acid) in the striatum of free-moving rats, as determined by means of brain microdialysis. Pretreatment with a voltage-dependent Na+ channel blocker, tetrodotoxin (TTX), lowered the basal level of 2,3-DHBA and strongly suppressed the increase in 2,3-DHBA induced by CO poisoning. CO poisoning significantly, though only slightly, increased extracellular glutamate in the striatum, and glutamate (Glu) receptor antagonists, such as MK-801 (dizocilpine) and NBQX, failed to suppress the CO-induced increase in 2,3-DHBA. These findings suggest that CO poisoning may induce Na+ influx via the voltage-dependent Na+ channels, resulting in stimulation of *OH generation in rat striatum. This effect may be independent of Glu receptor activation by increased extracellular Glu.
Hara
Shuichi
S
Department of Forensic Medicine, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku, Tokyo 160-8402, Japan. s-hara@tokyo-med.ac.jp
Mukai
Toshiji
T
Kurosaki
Kunihiko
K
Kuriiwa
Fumi
F
Endo
Takahiko
T
D000818:Animals; D002249:Carbon Monoxide Poisoning / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D062385:Hydroxybenzoates; D017665:Hydroxyl Radical / Q000378:metabolism*; D008297:Male; D017551:Microdialysis / Q000379:methods*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013779:Tetrodotoxin / Q000494:pharmacology; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; D062385:Hydroxybenzoates; D011810:Quinoxalines; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D017665:Hydroxyl Radical; D018698:Glutamic Acid; D013779:Tetrodotoxin; D016291:Dizocilpine Maleate; C009135:2,3-dihydroxybenzoic acid