Hatch R C, Laflamme D P, Jain A V
Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens 30602.
Vet Hum Toxicol. 1990 Feb;32(1):9-16.
To compare the protective potencies of a large number of known and potential cyanide antagonists in one stock of mice, groups (N = 10) of male CF-1 Swiss-Webster mice were given a single maximal or near-maximal intraperitoneal injection of each substance. Ethyl maleate, a glutathione (GSH) depletor and potential enhancer of cyanide toxicity, was given to other groups. Thirty min later, the mice were given subcutaneous injections of graded doses of KCN. In untreated control mice, the 24-hr median lethal dose (LD50) of KCN was 11 mg/kg of body weight (potency ratio, PR = 1.0). In comparison, protective effects of traditional antagonists thiosulfate and nitrite produced PR values of 1.48 and 2.95, respectively. Tetrathionate, sulfate, dithionite, methionine, hydroxocobalamin, ascorbate, pyridoxal phosphate, alpha-ketoglutarate, alpha-ketobutyrate, GSH, GSH disulfide (GSSG) and selenite were similar in efficacy to thiosulfate (P less than 0.05; PR values 1.35-1.59). Cysteine, diethyldithiocarbamate (DEDC), and cobaltous chloride were more effective than thiosulfate (PR values 1.68, 1.69, and 1.85, respectively). Phentolamine and dicobalt EDTA were ineffective, whereas papaverine enhanced toxicity (PR 0.72). Agents with significant PR values (greater than or equal to 1.14) but which were less effective than thiosulfate included sulfite, dimercaptosuccinic acid, pyruvate, citrate, alpha-ketovalerate, naloxone, and corn oil. Ethyl maleate in corn oil markedly enhanced KCN lethality (PR 0.57 compared to corn oil alone), and caused prolonged illness in several mice. Vitamin E in corn oil had no effect. Dual mixtures of thiosulfate with other selected substances were also tested.(ABSTRACT TRUNCATED AT 250 WORDS)
为了在一组小鼠中比较大量已知和潜在氰化物拮抗剂的保护效力，将雄性CF-1瑞士-韦伯斯特小鼠分成若干组（每组N = 10），每组小鼠腹腔注射每种物质一次，剂量为最大或接近最大剂量。向其他组小鼠注射马来酸乙酯，它是一种谷胱甘肽（GSH）消耗剂，也是氰化物毒性的潜在增强剂。30分钟后，给小鼠皮下注射不同剂量的KCN。在未处理的对照小鼠中，KCN的24小时半数致死剂量（LD50）为11毫克/千克体重（效力比，PR = 1.0）。相比之下，传统拮抗剂硫代硫酸盐和亚硝酸盐的保护作用产生的PR值分别为1.48和2.95。连四硫酸盐、硫酸盐、连二亚硫酸盐、蛋氨酸、羟钴胺素、抗坏血酸盐、磷酸吡哆醛、α-酮戊二酸、α-酮丁酸、GSH、GSH二硫化物（GSSG）和亚硒酸盐的效力与硫代硫酸盐相似（P < 0.05；PR值为1.35 - 1.59）。半胱氨酸、二乙基二硫代氨基甲酸盐（DEDC）和氯化钴比硫代硫酸盐更有效（PR值分别为1.68、1.69和1.85）。酚妥拉明和乙二胺四乙酸二钴无效，而罂粟碱增强了毒性（PR 0.72）。PR值显著（大于或等于1.14）但效力低于硫代硫酸盐的物质包括亚硫酸盐、二巯基琥珀酸、丙酮酸、柠檬酸盐、α-酮戊酸、纳洛酮和玉米油。玉米油中的马来酸乙酯显著增强了KCN的致死性（与单独的玉米油相比，PR为0.57），并使几只小鼠患病时间延长。玉米油中的维生素E没有效果。还测试了硫代硫酸盐与其他选定物质的二元混合物。（摘要截断于250字）
