Journal of Environmental Biology

         Protective role of alpha-ketoglutarate against massive doses of cyanide in rats

 

R. Bhattacharya and Rajkumar Tulsawani

Division of Pharmacology and Toxicology, Defence Research and Development Establishment,

Jhansi Road, Gwalior - 474 002, India

(Received: April 10, 2007; Revised received: November 12, 2007; Accepted: December 25, 2007)

 

Abstract: Cyanide is a highly toxic cellular poison that requires immediate and aggressive treatments. Combination of sodium nitrite (SN) and sodium thiosulfate (STS) is the treatment of choice but oral treatment of alpha-ketoglutarate (A-KG) has also been shown to significantly antagonize cyanide poisoning in laboratory animals. This study reports the efficacy of various treatment regimens as : (i) repeated doses of A-KG after simultaneous treatment of A-KG and STS, (ii) repeated doses of A-KG after pre-treatment of SN, STS and A-KG, (iii) repeated doses of STS after pre-treatment of SN, STS and A-KG, and (iv)  repeated doses of A-KG and STS after pre-treatment of SN, STS and A-KG on mortality of female rats exposed to massive doses of potassium cyanide. A maximum of 40-folds protection was observed when A-KG at 1.0 g kg^-1 after 2 hr and 0.5 g kg^-1 after 4 hr was repeated following the pre-treatment of SN (0.025 g kg^-1; subcutaneous; -45 min), STS (1.0 g kg^-1; intraperitoneal; -15 min)  and A-KG (2.0 g kg^-1; oral; -10 min). Similar protection was also conferred by repeating 0.5 g kg^-1 each of A-KG and STS 2 hr after pre-treatment of SN, STS and A-KG. Also, 38-folds protection after simultaneous administration of 2.0 g kg^-1 A-KG and 1.0 g kg^-1 STS, followed by 2.0 g kg^-1 A-KG after 2 hr was noteworthy. The results indicate that repeated treatment of A-KG alone after simultaneous treatment of A-KG and STS  or repeated treatment of A-KG alone or with STS after pre-treatment of A-KG, SN and STS have immense potential in challenging extremely high doses of cyanide as compared to the antidotes given once. The study has implications in the development of A-KG as an alternate treatment for cyanide poisoning. 

Key words: Cyanide, Toxicity, Protection, Alpha-ketoglutarate

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