Involvement of extracellular ascorbate and iron in hydroxyl radical generation in rat striatum in carbon monoxide poisoning.
Carbon monoxide (CO) poisoning stimulated generation in rat striatum of toxic hydroxyl radicals (*OH), which might participate in the CO-induced neuronal injury. Since an increase in extracellular ascorbate (AA) stimulated *OH generation in the presence of endogenous metals, including iron, in rat striatum in vivo, we examined the role of extracellular AA in *OH generation due to CO poisoning in the present study. The CO-induced *OH generation in the striatum was strongly suppressed by intrastriatal administration of active, but not inactivated, AA oxidase, which degrades extracellular AA. In addition, CO poisoning caused a significant increase in extracellular AA in rat striatum, suggesting a role of extracellular AA in the CO-induced *OH generation. However, the time-course of changes in extracellular AA could not be completely superimposed on that of the CO-induced *OH generation. On the other hand, the CO-induced *OH generation was completely suppressed by an iron chelator, deferoxamine. These findings suggest that *OH generation in rat striatum due to CO poisoning may involve both extracellular AA and chelatable iron.
Hara
Shuichi
S
Department of Forensic Medicine, Tokyo Medical University, Tokyo 160-8402, Japan. s-hara@tokyo-med.ac.jp
Mizukami
Hajime
H
Mukai
Toshiji
T
Kurosaki
Kunihiko
K
Kuriiwa
Fumi
F
Endo
Takahiko
T
D000641:Ammonia / Q000378:metabolism; D000818:Animals; D000975:Antioxidants; D001204:Ascorbate Oxidase / Q000494:pharmacology; D001205:Ascorbic Acid / Q000378:metabolism / Q000502:physiology*; D001923:Brain Chemistry / Q000187:drug effects; D002249:Carbon Monoxide Poisoning / Q000378:metabolism*; D002396:Catechols / Q000494:pharmacology; D062385:Hydroxybenzoates; D017665:Hydroxyl Radical / Q000378:metabolism*; D007501:Iron / Q000378:metabolism / Q000502:physiology*; D007502:Iron Chelating Agents / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013238:Stereotaxic Techniques
D000975:Antioxidants; D002396:Catechols; D062385:Hydroxybenzoates; D007502:Iron Chelating Agents; D017665:Hydroxyl Radical; C009135:2,3-dihydroxybenzoic acid; D000641:Ammonia; D007501:Iron; D001204:Ascorbate Oxidase; D001205:Ascorbic Acid