Hume A S, Mozingo J R, McIntyre B, Ho I K
University of Mississippi Medical Center, Jackson 39216, USA.
J Toxicol Clin Toxicol. 1995;33(6):721-4. doi: 10.3109/15563659509010637.
Alpha-ketoglutaric acid and sodium thiosulfate antagonize the toxic effects of cyanide. The present study was performed to test whether a synergistic effect may occur. The alpha-ketoglutaric acid/sodium thiosulfate solutions were injected intraperitoneally into mice prior to exposure to hydrogen cyanide (HCN) in a dynamic inhalation chamber or preceding an intraperitoneal injection of sodium cyanide (NaCN). All lethal concentration (LCT) and lethal dose (LD) values were determined after a period of 24 h. Alpha-ketoglutaric acid alone provided no protection at 250 mg/kg when challenged with HCN. Sodium thiosulfate 500 mg/kg provided a 5% protection. However, when these doses of alpha-ketoglutaric acid and sodium thiosulfate were combined, protection was increased by 18%. Alpha-ketoglutaric acid (250 mg/kg) and sodium thiosulfate (1000 mg/kg) provided an additional 48% protection against a LCT88 of HCN. A single dose of alpha-ketoglutaric acid (500 mg/kg) and sodium thiosulfate (1000 mg/kg) solutions afforded a 70% increase in survivability of the exposed animals. When mice were injected ip with 100 mg/kg of alpha-ketoglutaric acid 15 min prior to the injection of 5.5 mg/kg (LD50) of NaCN, the lethality was reduced to an LD30. Two hundred mg/kg alpha-ketoglutaric acid, challenged with the same dose of NaCN, reduced the lethality to 23%. When mice were challenged with 6.0 mg/kg of NaCN (LD70) pretreated with 100 mg/kg of alpha-ketoglutaric acid or 200 mg/kg of sodium thiosulfate, the LD was not altered in the former but reduced to an LD15 in the latter. At higher doses of sodium thiosulfate (500 mg/kg), an LD60 occurred at 13.6 mg/kg NaCN (2.5 x LD50).(ABSTRACT TRUNCATED AT 250 WORDS)
α-酮戊二酸和硫代硫酸钠可拮抗氰化物的毒性作用。本研究旨在测试是否可能产生协同效应。在动态吸入舱中让小鼠暴露于氰化氢（HCN）之前，或在腹腔注射氰化钠（NaCN）之前，将α-酮戊二酸/硫代硫酸钠溶液腹腔注射到小鼠体内。24小时后测定所有致死浓度（LCT）和致死剂量（LD）值。当用HCN攻击时，单独使用250mg/kg的α-酮戊二酸没有提供保护作用。500mg/kg的硫代硫酸钠提供了5%的保护作用。然而，当将这些剂量的α-酮戊二酸和硫代硫酸钠联合使用时，保护作用提高了18%。α-酮戊二酸（250mg/kg）和硫代硫酸钠（1000mg/kg）对HCN的LCT88提供了额外48%的保护作用。单剂量的α-酮戊二酸（500mg/kg）和硫代硫酸钠（1000mg/kg）溶液使暴露动物的存活率提高了70%。当小鼠在注射5.5mg/kg（LD50）的NaCN前15分钟腹腔注射100mg/kg的α-酮戊二酸时，致死率降至LD30。用相同剂量的NaCN攻击时，200mg/kg的α-酮戊二酸使致死率降至23%。当用100mg/kg的α-酮戊二酸或200mg/kg的硫代硫酸钠预处理小鼠，然后用6.0mg/kg的NaCN（LD70）攻击时，前者的LD未改变，而后者的LD降至LD15。在硫代硫酸钠更高剂量（500mg/kg）时，在13.6mg/kg的NaCN（2.5倍LD50）时出现LD60。（摘要截短至250字）
