用氯贝丁酯预处理使大鼠对低血糖素毒性产生抗性后的有机酸尿症。
Organic aciduria in rats made resistant to hypoglycin toxicity by pretreatment with clofibrate.
作者信息
Veitch R K, Sherratt H S, Bartlett K
机构信息
Department of Pharmacological Sciences, Medical School, University of Newcastle upon Tyne, U.K.
出版信息
Biochem J. 1987 Sep 15;246(3):775-8. doi: 10.1042/bj2460775.
Abstract
- The lethal, hypoglycaemic and hypothermic effects of hypoglycin in fasted rats are prevented if the rats had been fed on a diet containing clofibrate (0.5% w/w). 2. Injection of hypoglycin into fasted rats maintained on a standard diet caused severe prostration, hypothermia and a massive dicarboxylic aciduria [Tanaka (1972) J. Biol. Chem. 247, 7465-7478]. 3. Rats maintained on a diet containing clofibrate appeared normal after injection of hypoglycin, but had a marked dicarboxylic aciduria which was less than that induced in rats on a normal diet. 4. After administration of hypoglycin, butyryl-CoA and decanoyl-CoA, but not palmitoyl-CoA, dehydrogenase activities were strongly inhibited (80-95%) in the livers of animals on a standard diet. 5. Clofibrate feeding decreased the inhibition of these dehydrogenases to about 40-60%. 6. It was concluded that although clofibrate protects against the toxic effects of hypoglycin, some enzyme inhibitions as indicated by dicarboxylic aciduria are only partly prevented.
摘要
- 如果大鼠喂食含氯贝丁酯（0.5% w/w）的日粮，低血糖素对禁食大鼠的致死、降血糖和体温过低作用可被预防。2. 给维持标准日粮的禁食大鼠注射低血糖素会导致严重虚脱、体温过低和大量二羧酸尿症[田中（1972年）《生物化学杂志》247卷，7465 - 7478页]。3. 喂食含氯贝丁酯日粮的大鼠注射低血糖素后看似正常，但有明显的二羧酸尿症，且比正常日粮喂养的大鼠所诱导的二羧酸尿症要少。4. 给予低血糖素后，标准日粮喂养动物肝脏中的丁酰辅酶A和癸酰辅酶A脱氢酶活性受到强烈抑制（80 - 95%），但棕榈酰辅酶A脱氢酶活性未受抑制。5. 喂食氯贝丁酯可使这些脱氢酶的抑制作用降至约40 - 60%。6. 得出的结论是，虽然氯贝丁酯可防止低血糖素的毒性作用，但二羧酸尿症所表明的一些酶抑制作用仅得到部分预防。
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