Isom G E, Way J L
Toxicol Appl Pharmacol. 1984 Jun 15;74(1):57-62. doi: 10.1016/0041-008x(84)90269-2.
Since oxygen was reported to be an effective cyanide antagonist in vivo, particularly in the presence of the classic antidotal combination of sodium nitrite and sodium thiosulfate, in vitro studies were initiated in an attempt to investigate the mechanism of oxygen-mediated cyanide antagonism. The effect of oxygen on cyanide-inhibited cytochrome oxidase with and without cyanide antagonist(s) was investigated in a purified membraneous enzyme system prepared from rat liver mitochondria. Cyanide produced a concentration dependent inhibition of cytochrome oxidase, and 100% oxygen did not alter the inhibition produced by KCN either in the presence or absence of sodium thiosulfate. However, the addition of sodium thiosulfate and rhodanese to the assay reactivated the cyanide-inhibited cytochrome oxidase. Kinetic analysis indicated rhodanese competes with cytochrome oxidase for cyanide, and oxygen had no effect on this coupled reaction. In conclusion, the in vivo antidotal properties of oxygen cannot be attributed to oxygen-mediated reactivation of cyanide-inhibited cytochrome oxidase or an oxygen-mediated acceleration of rhodanese detoxification.
由于据报道氧气在体内是一种有效的氰化物拮抗剂，特别是在存在亚硝酸钠和硫代硫酸钠这种经典解毒组合的情况下，因此开展了体外研究，试图探究氧气介导的氰化物拮抗作用机制。在由大鼠肝线粒体制备的纯化膜酶系统中，研究了有无氰化物拮抗剂时氧气对氰化物抑制的细胞色素氧化酶的影响。氰化物对细胞色素氧化酶产生浓度依赖性抑制，并且无论有无硫代硫酸钠，100%的氧气都不会改变氰化钾产生的抑制作用。然而，在测定中加入硫代硫酸钠和硫氰酸酶可使被氰化物抑制的细胞色素氧化酶重新激活。动力学分析表明，硫氰酸酶与细胞色素氧化酶竞争氰化物，而氧气对这种偶联反应没有影响。总之，氧气在体内的解毒特性不能归因于氧气介导的被氰化物抑制的细胞色素氧化酶的重新激活，也不能归因于氧气介导的硫氰酸酶解毒作用的加速。
