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.