Role of mitochondrial respiratory chain in neuronal toxicity due to carbon monoxide poisoning

线粒体反应链是细胞中与反应性氧物种（ROS）生成相关的途径之一。这一链结果在ROS生成刺激中的中断。在这一研究中，我们研究了甲基氯离子反应链与羟基基础（·OH）在碳单氧化物（CO）中毒的含义是脑微分析中产生的，因为CO抑制了反应链中的复合物IV。MPP^+ （complex I inhibitor）、malonate （complex II inhibitor）和NaCN （complex IV inhibitor， like CO）刺激·OH generation in rat striatum by themselves。一氧化碳与MPP^+或NaCN结合，结果是在·OH产生的附加潜力中，同时一氧化碳和麦芽糖结合治疗的影响。NaCN在与malonate结合时没有这样的同步效应，建议CO产生OH的同步潜力，而malonate可能会从CO的行为中产生其他的抑制作用。在另一方面，CO-诱导·OH生成被硝酸氧化物（NO）合成酶（NOS）抑制剂、N^G-硝基-L-精氨酸甲基酯和N^G-单甲基-L-精氨酸抑制剂抑制和潜在，相应地。这些NOS抑制剂的影响受到了无前体、L-精氨酸的关注，而D-精氨酸的强烈刺激了CO-诱导的OH产生在NOS抑制剂的存在中。这些发现提出了CO-诱导的·OH生成可能是由复杂机制介导的。如果没有参与机制， NOS，但不是每秒钟，你可以扮演一个角色。还有一个对mitochondiral repiratory chain的不修改，它是不明确的，因为没有在CO和malonate的合成潜力中发挥作用。

The mitochondrial respiration chain is one of pathways associated with reactive oxygen species (ROS) generation in the cell. Interruption of this chain results in stimulation of ROS generation. In this study, it was examined whether the mitochondrial respiration chain was associated with hydroxyl radical (・OH) generation in rat striatum in carbon monoxide (CO) poisoning by means of brain microdialysis, since CO inhibits the complex IV in the respiratory chain. MPP^+ (complex I inhibitor), malonate (complex II inhibitor) and NaCN (complex IV inhibitor, like CO) stimulated ・OH generation in rat striatum by themselves. CO in combination with MPP^+ or NaCN resulted in the additive potentiation of ・OH generation, while the effect of the combined treatment with CO and malonate was synergistical. NaCN had no such synergistic effect when combined with malonate, suggesting that the synergistic potentiation of ・OH generation by CO and malonate may be derived from CO actions other than the inhibition of the complex IV. On the other hand, the CO-induced ・OH generation was suppressed and potentiated by nitric oxide (NO) synthase (NOS) inhibitors, N^G-nitro-L-arginine methyl ester and N^G-monomethyl-L-arginine, respectively. The effects of these NOS inhibitors were attenuated by the NO precursor, L-arginine, while D-arginine strongly stimulated the CO-induced ・OH generation in the presence of NOS inhibitors. These findings suggest that the CO-induced ・OH generation may be mediated by complex mechanisms. If NO participates in the mechanisms, NOS, but not NO per se, might play a role. Although NO modifies the mitochondiral repiratory chain, it is unclear whether NO plays a role in the synergistic potentiation in ・OH generation by CO and malonate.