Hara Shuichi, Mizukami Hajime, Mukai Toshiji, Kurosaki Kunihiko, Kuriiwa Fumi, Endo Takahiko
Department of Forensic Medicine, Tokyo Medical University, Tokyo 160-8402, Japan.
Toxicology. 2009 Oct 1;264(1-2):69-73. doi: 10.1016/j.tox.2009.07.010. Epub 2009 Jul 24.
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.
一氧化碳（CO）中毒可刺激大鼠纹状体产生毒性羟基自由基（OH），这些自由基可能参与了CO诱导的神经元损伤。由于细胞外抗坏血酸（AA）的增加会在体内大鼠纹状体中在内源性金属（包括铁）存在的情况下刺激OH的产生，因此在本研究中我们考察了细胞外AA在CO中毒导致的OH产生中的作用。纹状体内注射可降解细胞外AA的活性（而非失活的）AA氧化酶，可强烈抑制CO诱导的纹状体OH产生。此外，CO中毒导致大鼠纹状体细胞外AA显著增加，提示细胞外AA在CO诱导的OH产生中发挥作用。然而，细胞外AA变化的时间进程并不能完全与CO诱导的OH产生的时间进程相重叠。另一方面，铁螯合剂去铁胺可完全抑制CO诱导的OH产生。这些发现表明，CO中毒导致的大鼠纹状体OH产生可能涉及细胞外AA和可螯合铁。
