PROLONGED HYPOLACTATEMIA AND INCREASED TOTAL PYRUVATE-DEHYDROGENASE ACTIVITY BY DICHLOROACETATE
PROLONGED HYPOLACTATEMIA AND INCREASED TOTAL PYRUVATE-DEHYDROGENASE ACTIVITY BY DICHLOROACETATE
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DOI：
10.1016/0006-2952(82)90019-3
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发表时间：
1982-01-01
影响因子：
5.8
通讯作者：
STACPOOLE, PW
中科院分区：
文献类型：
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作者：
EVANS, OB;STACPOOLE, PW
二氯乙酸盐（DCA）作为单剂量灌胃给予健康的进食大鼠，引起血糖、乳酸盐和丙酮酸盐的一过性降低。长期每日给药导致这些代谢物降低，并延迟乳酸盐恢复至基础水平，持续至末次给药后48小时。急性多次给药或慢性每日给药，DCA引起丙酮酸脱氢酶复合物（PDHC）活化。活性PDHC升高持续至末次给药后12 h。此外，总PDHC活性随着长期给药而增加，并在末次给药后持续48小时。这种增加不被蛋白质合成抑制剂阻断。DCA增加了分离的肝细胞[14 C-1]丙酮酸氧化和激活的肝细胞PDHC。乙醛酸和草酸，DCA的肝脏代谢产物，在相似的浓度下具有抑制作用。
Dichloroacetate (DCA) given gastrically as a single dose to healthy, fed rats caused transient lowering of blood glucose, lactate and pyruvate. Chronic daily dosing caused lowering of these metabolites and a delay in the return of lactate to basal levels for 48 h after the final dose. DCA caused activation of the pyruvate dehydrognease complex (PDHC), with acute multiple dosing or chronic daily dosing. The elevated active PDHC persisted for 12 h following the final dose. In addition, total PDHC activity was increased with chronic dosing and persisted for 48 h following the final dose. This increase was not blocked by protein synthesis inhibitors. DCA increased isoalted hepatocyte [14C-1]pyruvate oxidation and activated hepatocyte PDHC. Glyoxylate and oxalate, hepatic metabolites of DCA, were inhibitory at similar concentrations.