title: Existence of a threshold for hydroxyl radical generation independent of hypoxia in rat striatum during carbon monoxide poisoning.
abstract: We examined the role of hypoxia in the carbon monoxide (CO)-induced generation of the hydroxyl radical (•OH) in the striatum, which could contribute to brain damage due to CO poisoning. Exposure of free-moving rats to 1,000 and 3,000 ppm CO or 8 and 5% O2 for 40 min caused concentration-dependent hypoxic conditions in terms of carboxyhemoglobin (COHb), deoxyhemoglobin, oxyhemoglobin, and O2 contents in arterial blood. The hypoxic conditions seemed comparable between 3,000 ppm CO and 5% O2, although alterations of pH and partial O2 pressure (PO2) were complex and concentration independent. In the striatum, CO and low O2 decreased tissue PO2 levels in a concentration-dependent and concentration-independent manner, respectively, but levels at the end of exposure were comparable among all groups. This was also the case for the increase in striatal blood flow. Although the increases in extracellular glutamate (excitatory), taurine (inhibitory), and alanine (non-neurotransmitter), in the striatum in response to CO and low O2 were complex, 3,000 ppm CO and 5% O2 had comparable effects. Thus, 3,000 ppm CO and 5% O2 seemed to induce comparable hypoxic conditions. Nevertheless, the former more strongly stimulated (•OH generation in the striatum than the latter. In addition, in contrast to low O2 which caused a concentration-dependent increase in (•OH, 1,000 ppm CO had no effect. The findings suggest that striatal •OH generation due to CO poisoning may be independent of hypoxia per se and that a threshold might exist.
authors.affiliation: Department of Forensic Medicine, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo, 160-8402, Japan. s-hara@tokyo-med.ac.jp
authors.forename: Shuichi
authors.initials: S
authors.lastname: Hara
authors.forename: Hajime
authors.initials: H
authors.lastname: Mizukami
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Kurosaki
authors.forename: Fumi
authors.initials: F
authors.lastname: Kuriiwa
authors.forename: Toshiji
authors.initials: T
authors.lastname: Mukai
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D002248:Carbon Monoxide / Q000633:toxicity; D002249:Carbon Monoxide Poisoning / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D003342:Corpus Striatum / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D017665:Hydroxyl Radical / Q000378:metabolism*; D000860:Hypoxia / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D017551:Microdialysis; D010100:Oxygen / Q000378:metabolism; D010313:Partial Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000596:Amino Acids; D017665:Hydroxyl Radical; D002248:Carbon Monoxide; D010100:Oxygen