Department of Hygiene and Public Health, Osaka Medical College, Osaka, Japan.
Drug Chem Toxicol. 2009;32(4):353-61. doi: 10.1080/01480540903170720.
Sodium monofluoroacetate (SMFA; also known as compound 1080) is a highly toxic chemical; therefore, accidental exposure and intentional misuse are of great concern. SMFA intoxication is reportedly caused by the inhibition of aconitase. However, the pathogenesis underlying SMFA intoxication is not clear. This study was conducted to elucidate the acute effects of SMFA on glucose, amino-acid, and fatty-acid metabolism and to assess glucose supplementation as a possible alleviator or aggravator in SMFA intoxication. Rats were assigned to three groups: SMFA+saline, SMFA+glucose, and control (i.e., no SMFA), and blood samples were analyzed at 3 hours after SMFA or saline (control) administration. Additional rats were used for the monitoring of blood-glucose and lactate concentrations for 10 hour- and 14-day survival rates. SMFA increased the serum-citrate, serum-pyruvate, and blood-lactate concentrations. However, despite significant increases in these parameters when SMFA was administered with glucose, the effects on pH values were small and the survival rate was not changed. SMFA also increased the serum concentrations of free fatty acids, branched-chain amino acids, ammonia, urea, and calcium. The presence of glucose enhanced or suppressed these metabolic changes. Amphibolic intermediates in the tricarboxylic acid cycle might be supplied through the catabolism of proteins in SMFA intoxication. We conclude that other factors, in addition to the accumulation of lactate, citrate, and pyruvate, may affect survival rates, and that SMFA induces imbalances in glucose, amino-acid, and, fatty-acid metabolism. All these changes are inter-related and may contribute to SMFA intoxication.
单氟乙酸钠（SMFA；也称为化合物 1080）是一种剧毒化学品；因此，意外接触和故意滥用都令人十分担忧。据报道，SMFA 中毒是由乌头酸酶抑制引起的。然而，SMFA 中毒的发病机制尚不清楚。本研究旨在阐明 SMFA 对葡萄糖、氨基酸和脂肪酸代谢的急性影响，并评估葡萄糖补充作为 SMFA 中毒的一种可能的缓解或加重因素。将大鼠分为三组：SMFA+盐水、SMFA+葡萄糖和对照组（即无 SMFA），并在 SMFA 或盐水（对照）给药后 3 小时分析血液样本。还使用了额外的大鼠来监测血糖和乳酸浓度 10 小时和 14 天的存活率。SMFA 增加了血清柠檬酸、血清丙酮酸和血液乳酸浓度。然而，尽管当 SMFA 与葡萄糖一起给药时，这些参数显著增加，但对 pH 值的影响很小，存活率没有改变。SMFA 还增加了血清游离脂肪酸、支链氨基酸、氨、尿素和钙的浓度。葡萄糖的存在增强或抑制了这些代谢变化。三羧酸循环中的两栖中间体可能通过 SMFA 中毒时蛋白质的分解代谢提供。我们得出结论，除了乳酸、柠檬酸和丙酮酸的积累外，其他因素可能会影响存活率，并且 SMFA 会导致葡萄糖、氨基酸和脂肪酸代谢失衡。所有这些变化都是相互关联的，可能导致 SMFA 中毒。
