Tordon® is the commercial name of a mixture of two organo-chlorinated herbicides, 2,4-D and picloram. Both compounds affect energy transduction in isolated mitochondria and the present study aimed at characterizing the actions of these two compounds on liver metabolism and their cellular distribution in the isolated perfused rat liver. 2,4-D, but not picloram, increased glycolysis in the range from 10 to 400 μM. The redox potential of the cytosolic NAD+-NADH couple was also increased by 2,4-D. Both compounds inhibited lactate gluconeogenesis. Inhibitions by 2,4-D and picloram were incomplete, reaching maximally 46% and 23%, respectively. Both compounds diminished the cellular ATP levels. No synergism between the actions of 2,4-D and picloram was detected. Biotransformations of 2,4-D and picloram were slow, but their distributions occurred at high rates and were concentrative. Molecular dynamics simulations revealed that 2,4-D presented low affinity for the hydrophobic lipid bilayers, the opposite occurring with picloram. Inhibition of energy metabolism is possibly a relevant component of the toxicity of 2,4-D and of the commercial product Tordon®. Furthermore, the interactions of 2,4-D with the membrane lipid bilayer can be highly destructive and might equally be related to its cellular toxicity at high concentrations.

中文翻译：

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有机氯化除草剂 2,4-D 和毒莠定在肝脏中的代谢效应、分布空间和脂双层亲和力的动力学

Tordon® 是两种有机氯化除草剂 2,4-滴 和 picloram 的混合物的商业名称。这两种化合物都会影响离体线粒体中的能量转导，本研究旨在表征这两种化合物对肝脏代谢的作用及其在离体灌注大鼠肝脏中的细胞分布。2,4-D，但不是毒莠定，在 10 到 400 μM 的范围内增加糖酵解。胞质 NAD+-NADH 对的氧化还原电位也增加了 2,4-D。两种化合物均抑制乳酸糖异生。2,4-D 和毒莠定的抑制作用不完全，分别达到最大 46% 和 23%。这两种化合物都降低了细胞 ATP 水平。未检测到 2,4-D 和毒莠定的作用之间的协同作用。2,4-D 和 picloram 的生物转化缓慢，但它们的分布发生率很高并且很集中。分子动力学模拟表明，2,4-D 对疏水性脂质双层具有低亲和力，而毒莠定则相反。能量代谢的抑制可能是 2,4-D 和商业产品 Tordon® 毒性的相关组成部分。此外，2,4-D 与膜脂双层的相互作用可能具有高度破坏性，并且可能同样与其在高浓度下的细胞毒性有关。