Di Padova M, Barbieri R, Fanciulli M, Arcuri E, Floridi A
Laboratory of Cell Metabolism and Pharmacokinetics, Regina Elena Institute for Cancer Research, Rome, Italy.
Oncol Res. 1998;10(10):491-8.
The effect of local anesthetic ropivacaine on the energy metabolism of Ehrlich ascites tumor cells has been investigated. Ropivacaine impaired energy metabolism of Ehrlich ascites tumor cells by affecting primarily mitochondrial metabolism. Even at low concentrations ropivacaine decreased the rate of oxygen uptake, but its effect was remarkably higher on the uncoupled respiration and, in both cases, it was strongly enhanced by hydrophobic anion tetraphenylboron (TPB-). The decrease of oxygen uptake was ascribed to an impairment of electron transport from site 1- and 2-entering substrates to respiratory chain. The inhibition of respiration, coupled to a true uncoupling mechanism by an electrophoretic mechanism, impaired ADP phosphorylation, decreased ATP content, and collapsed mitochondrial membrane potential. Ropivacaine, at all concentrations tested, stimulated aerobic lactate production, and this increase, in addition to the inhibition of respiration, was also due to an activation of mitochondrial ATPase.
研究了局部麻醉药罗哌卡因对艾氏腹水癌细胞能量代谢的影响。罗哌卡因主要通过影响线粒体代谢来损害艾氏腹水癌细胞的能量代谢。即使在低浓度下,罗哌卡因也会降低氧气摄取率,但其对解偶联呼吸的影响显著更高,在这两种情况下,疏水性阴离子四苯基硼(TPB-)都会强烈增强其作用。氧气摄取的减少归因于从位点1和2进入底物到呼吸链的电子传递受损。呼吸抑制通过电泳机制与真正的解偶联机制相结合,损害了ADP磷酸化,降低了ATP含量,并使线粒体膜电位崩溃。在所有测试浓度下,罗哌卡因都刺激了有氧乳酸的产生,除了抑制呼吸外,这种增加还归因于线粒体ATP酶的激活。