Lock E A, Gyte A, Widdowson P, Simpson M, Wyatt I
Neurotoxicology Group, Zeneca Central Toxicology Laboratory, Cheshire, UK.
Arch Toxicol. 1995;69(9):640-3. doi: 10.1007/s002040050225.
We have examined the effect of L- and D-2-chloropropionic acid (L-CPA and D-CPA) on the concentrations of pyruvate, lactate, glucose and beta-hydroxybutyrate in the blood at various times after doses which produce cerebellar granule cell necrosis. Blood pyruvate and lactate concentrations were reduced in these animals 4 h after dosing and remained below those of controls for up to 48 h. No changes were seen in concentrations of plasma glucose of beta-hydroxybutyrate at any time point. Similarly, no changes in cerebellar glucose, pyruvate or lactate were seen 24 h after 750 mg/kg L-CPA. Oxidation of [14C] pyruvate or [14C] glucose to [14CO2] by cerebellar slices from control rats was not altered by the presence of L- or D-CPA (1-10 mM for 2 h). Nor were these parameters affected in cerebellar slices from rats killed 24 h after a dose of 750 mg/kg L-CPA. We conclude that the activation of the pyruvate dehydrogenase complex is unlikely to be a critical factor in the selective toxicity of CPA to the cerebellum.
我们研究了左旋和右旋2-氯丙酸（L-CPA和D-CPA）在产生小脑颗粒细胞坏死的剂量给药后不同时间对血液中丙酮酸、乳酸、葡萄糖和β-羟基丁酸浓度的影响。给药后4小时，这些动物血液中的丙酮酸和乳酸浓度降低，并且在长达48小时内一直低于对照组。在任何时间点，血浆葡萄糖或β-羟基丁酸的浓度均未出现变化。同样，给予750mg/kg L-CPA 24小时后，小脑葡萄糖、丙酮酸或乳酸未见变化。对照大鼠小脑切片将[14C]丙酮酸或[14C]葡萄糖氧化为[14CO2]的过程，不受L-或D-CPA（1-10mM，处理2小时）存在的影响。给予750mg/kg L-CPA剂量24小时后处死的大鼠的小脑切片中，这些参数也未受影响。我们得出结论，丙酮酸脱氢酶复合体的激活不太可能是CPA对小脑选择性毒性的关键因素。
