Moore S J, Norris J C, Ho I K, Hume A S
Toxicol Appl Pharmacol. 1986 Jan;82(1):40-4. doi: 10.1016/0041-008x(86)90435-7.
It has been reported that compounds containing carbonyl groups can readily react with cyanide. Pyruvic acid, an alpha-ketocarboxylic acid, has been shown to antagonize the lethal effects of cyanide. It is suggested that its mechanism of action rests in its ability to react with or "bind" cyanide. In this study, alpha-ketoglutaric acid, also an alpha-ketocarboxylic acid, was evaluated for its ability to counteract the lethal effects of cyanide. alpha-Ketoglutaric acid increased the LD50 value of cyanide (6.7 mg/kg) by a factor of five, a value statistically equivalent to that ascertained in mice pretreated with sodium thiosulfate and sodium nitrite. The combination of alpha-ketoglutaric acid and sodium thiosulfate increased the LD50 value of cyanide to 101 mg/kg. Addition of sodium nitrite to the alpha-ketoglutaric acid/sodium thiosulfate regimen increased the LD50 value of cyanide to 119 mg/kg. Unlike sodium nitrite, no induction of methemoglobin formation was observed with alpha-ketoglutaric acid pretreatment. It is apparent from these studies that the administration of alpha-ketoglutaric acid in conjunction with sodium thiosulfate resulted in fewer animal deaths than sodium nitrite and sodium thiosulfate without the dangerous formation of methemoglobin.
据报道，含羰基的化合物能很容易地与氰化物发生反应。丙酮酸，一种α-酮羧酸，已被证明可拮抗氰化物的致死作用。有人认为其作用机制在于它与氰化物反应或“结合”氰化物的能力。在本研究中，α-酮戊二酸，也是一种α-酮羧酸，被评估其对抗氰化物致死作用的能力。α-酮戊二酸使氰化物的半数致死量（LD50）值（6.7毫克/千克）提高了五倍，该值在统计学上与用硫代硫酸钠和亚硝酸钠预处理的小鼠中所确定的值相当。α-酮戊二酸和硫代硫酸钠的组合使氰化物的LD50值提高到101毫克/千克。在α-酮戊二酸/硫代硫酸钠方案中加入亚硝酸钠使氰化物的LD50值提高到119毫克/千克。与亚硝酸钠不同，α-酮戊二酸预处理未观察到高铁血红蛋白形成的诱导。从这些研究中可以明显看出，与亚硝酸钠和硫代硫酸钠相比，联合使用α-酮戊二酸和硫代硫酸钠导致动物死亡更少，且不会形成危险的高铁血红蛋白。
