Bhattacharya R, Tulsawani Rajkumar
Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior-474 002, India.
J Environ Biol. 2009 Jul;30(4):515-20.
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.
氰化物是一种剧毒的细胞毒素，需要立即进行积极治疗。亚硝酸钠（SN）和硫代硫酸钠（STS）联合使用是首选治疗方法，但在实验动物中，口服α-酮戊二酸（A-KG）也已显示出能显著对抗氰化物中毒。本研究报告了以下各种治疗方案的疗效：（i）在同时给予A-KG和STS后重复给予A-KG；（ii）在预先给予SN、STS和A-KG后重复给予A-KG；（iii）在预先给予SN、STS和A-KG后重复给予STS；（iv）在预先给予SN、STS和A-KG后重复给予A-KG和STS，观察其对暴露于大剂量氰化钾的雌性大鼠死亡率的影响。在预先给予SN（0.025 g kg⁻¹；皮下注射；-45分钟）、STS（1.0 g kg⁻¹；腹腔注射；-15分钟）和A-KG（2.0 g kg⁻¹；口服；-10分钟）后，2小时后给予1.0 g kg⁻¹的A-KG，4小时后给予0.5 g kg⁻¹的A-KG，观察到最大40倍的保护作用。在预先给予SN、STS和A-KG后2小时，重复给予0.5 g kg⁻¹的A-KG和STS，也能提供类似的保护作用。同样，在同时给予20 g kg⁻¹的A-KG和1.0 g kg⁻¹的STS，然后在2小时后给予2.0 g kg⁻¹的A-KG后，观察到38倍的保护作用也值得注意。结果表明，与单次给予解毒剂相比，在同时给予A-KG和STS后重复单独给予A-KG，或在预先给予A-KG、SN和STS后重复单独给予A-KG或与STS联合使用，在对抗极高剂量的氰化物方面具有巨大潜力。该研究对将A-KG开发为氰化物中毒的替代治疗方法具有重要意义。
