SIGNIFICANCE OF SULFHYDRYL COMPOUNDS IN THE MANIFESTATION OF FLUOROACETATE TOXICITY TO THE RAT, BRUSH-TAILED POSSUM, WOYLIE AND WESTERN GREY-KANGAROO
SIGNIFICANCE OF SULFHYDRYL COMPOUNDS IN THE MANIFESTATION OF FLUOROACETATE TOXICITY TO THE RAT, BRUSH-TAILED POSSUM, WOYLIE AND WESTERN GREY-KANGAROO
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DOI：
10.1071/bi9850139
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发表时间：
1985-01-01
期刊：
影响因子：
--
通讯作者：
TWIGG, LE
中科院分区：
文献类型：
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作者：
MEAD, RJ;MOULDEN, DL;TWIGG, LE
正常谷胱甘肽水平大鼠的肾脏和肝脏中的柠檬酸水平在每公斤体重给予1.5 mg化合物1080（= 95%氟乙酸钠）2小时后分别增加6.8倍和1.7倍。在肝脏谷胱甘肽水平为正常水平15%的动物中，氟乙酸给药后血浆和肝脏中的柠檬酸水平的增加明显大于对照动物。半胱胺和n -乙酰半胱氨酸与谷胱甘肽一样，在大鼠肝脏制剂中部分保护乌头酸水合酶免受氟柠檬酸抑制，但在体外实验中不能取代谷胱甘肽作为氟乙酸脱氟的底物。n -乙酰半胱氨酸没有降低谷胱甘肽缺乏大鼠的血浆柠檬酸水平，而半胱胺抑制谷胱甘肽缺乏的刷尾负鼠的体内去氟率。非生理性巯基化合物是体内氟乙酸中毒的无效解毒剂。对氟乙酸具有不同敏感性的4种哺乳动物的体内脱氟模式并未表明耐受性与脱氟率之间存在直接关系，同时也表明，负责氟乙酸脱氟的谷胱甘肽- s转移酶的高水平活性并非耐药哺乳动物规避氟乙酸毒性的主要机制。
Levels of citrate in kidneys and livers of rats with normal glutathione levels increased 6.8- and 1.7-fold respectively 2 h after dosing with 1.5 mg of compound 1080 (= 95% sodium fluoroacetate) per Kg body wt. In animals with liver glutathione levels 15% of normal, increases in plasma and liver citrate levels after dosing with fluoroacetate were significantly greater than those of control animals. Cysteamine and N-acetylcysteine, like glutathione, partially protected aconitate hydratase from fluorocitrate inhibition in rat liver preparations but were unable to replace glutathione as a substrate for the defuluorination of fluoroacetate in vitro. N-Acetylcysteine did not diminish plasma citrate levels of glutathione-deficient rats dosed with fluoroacetate, while cysteamine inhibited the rate of in vivo defluorination in glutathione-deficient brush-tailed possums. Non-physiological sulfhydryl compounds are ineffective antidotes to fluoroacetate intoxication in vivo. The in vivo defluorination patterns of 4 mammal species with differing sensitivities of fluoroacetate did not indicate a direct relationship between tolerance and rate of defluorination and its is also suggested that a high level of activity of the glutathione-S-transferase responsible for the defluorination of fluoroacetate is not the major mechanism for circumventing fluoroacetate toxicity in resistant mammals.