Kuriiwa Fumi, Kobayashi Masamune, Mizukami Hajime, Hara Shuichi
Department of Forensic Medicine, Tokyo Medical University, Tokyo 160-8402, Japan.
Department of Legal Medicine, Kanazawa Medical University, Ishikawa 920-0293, Japan.
J Pharmacol Sci. 2021 May;146(1):29-32. doi: 10.1016/j.jphs.2021.02.008. Epub 2021 Mar 4.
Hydroxyl radical (OH) production in the rat striatum during carbon monoxide (CO) poisoning, which inhibits complex IV, was enhanced synergistically by malonate, a mitochondrial complex II inhibitor, but not N-methyl-4-phenylpyridinium or NaCN, complex I and IV inhibitors, respectively. No such enhancement appeared in the case of NaCN combined with malonate. Intrastriatal dopamine, which is involved in OH production by malonate, did not synergistically enhance CO-induced OH production. Diphenyleneiodonium, a nonselective NADPH oxidase inhibitor, partly suppressed the potentiation of CO-induced OH production by malonate. Impairment of mitochondrial functions might potentiate oxidative stress and intensify CO toxicity in the brain.
一氧化碳（CO）中毒期间大鼠纹状体中羟基自由基（OH）的产生受到抑制，这是因为CO抑制了复合物IV。线粒体复合物II抑制剂丙二酸可协同增强OH的产生，但复合物I和IV抑制剂N-甲基-4-苯基吡啶鎓或NaCN则无此作用。NaCN与丙二酸联合使用时未出现这种增强作用。参与丙二酸诱导OH产生的纹状体内多巴胺，并不会协同增强CO诱导的OH产生。非选择性NADPH氧化酶抑制剂二亚苯基碘鎓可部分抑制丙二酸对CO诱导的OH产生的增强作用。线粒体功能受损可能会增强氧化应激并加剧大脑中的CO毒性。
