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

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 pretreatment 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.