Bhattacharya R, Vijayaraghavan R
Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior, India.
Biomed Environ Sci. 1991 Dec;4(4):452-60.
Antagonising effects of alpha-ketoglutarate (alpha-KG) could be attributed to complexing of the reactive nucleophile (CN-) to form cyanohydrin in cyanide intoxication. However, an enormous protection obtained could not be delineated on account of possible in situ binding of alpha-KG given intraperitoneally (i.p.) in mice to cyanide administered through the same route. The present study was designed to see the efficacy of alpha-KG alone or in combination with sodium nitrite (SN) and/or sodium thiosulfate (STS) in male mice exposed to cyanide administered through subcutaneous (s.c.) or inhalation route. A technique for generation of hydrogen cyanide (HCN) is also discussed. On the basis of protection index (PI), defined here as the LD50 of cyanide in protected mice/LD50 of cyanide in unprotected mice and survival time, STS + alpha-KG regimen was equipotent to the conventional SN + STS regimen. This is further substantiated by effect of alpha-KG in reducing plasma cyanide levels. The efficacy of alpha-KG remains undeterred irrespective of the route of cyanide intoxication, while the magnitude of protection varies.
α-酮戊二酸（α-KG）的拮抗作用可能归因于在氰化物中毒时，活性亲核试剂（CN-）与之络合形成氰醇。然而，由于腹腔注射（i.p.）给小鼠的α-KG可能与经相同途径给予的氰化物发生原位结合，因而无法确定所获得的巨大保护作用。本研究旨在观察单独使用α-KG或与亚硝酸钠（SN）和/或硫代硫酸钠（STS）联合使用时，对经皮下（s.c.）或吸入途径给予氰化物的雄性小鼠的疗效。还讨论了一种生成氰化氢（HCN）的技术。基于在此定义为受保护小鼠中氰化物的半数致死量（LD50）/未受保护小鼠中氰化物的半数致死量（LD50）的保护指数（PI）和存活时间，STS + α-KG方案与传统的SN + STS方案等效。α-KG降低血浆氰化物水平的作用进一步证实了这一点。无论氰化物中毒途径如何，α-KG的疗效均不受影响，只是保护程度有所不同。
