Protective role of alpha-ketoglutarate against massive doses of cyanide in rats.
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) andA-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 20 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.
Bhattacharya
R
R
Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior-474 002, India.
Tulsawani
Rajkumar
R
D000818:Animals; D005260:Female; D007656:Ketoglutaric Acids / Q000008:administration & dosage / Q000494:pharmacology*; D011042:Poisons / Q000008:administration & dosage / Q000633:toxicity*; D011190:Potassium Cyanide / Q000008:administration & dosage / Q000633:toxicity*; D020011:Protective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012977:Sodium Nitrite / Q000008:administration & dosage / Q000494:pharmacology; D013885:Thiosulfates / Q000008:administration & dosage / Q000494:pharmacology
D007656:Ketoglutaric Acids; D011042:Poisons; D020011:Protective Agents; D013885:Thiosulfates; C017717:sodium thiosulfate; D012977:Sodium Nitrite; D011190:Potassium Cyanide