Cyanide intoxication in mice through different routes and its prophylaxis by alpha-ketoglutarate

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.