Szelag Adam, Magdalan Jan, Rutkowska Maria, Dziewiszek Wojciech, Trocha Małgorzata, Rzepka Małgorzata, Pieśniewska Małgorzata, Fereniec Lidia
Department of Pharmacology, Medical University of Wrocław, Mikulicza-Radeckiego 2, PL 50-345 Wrocław, Poland.
Pol J Pharmacol. 2003 Mar-Apr;55(2):203-8.
An increase in calcium ion concentration in the cytoplasm due to the influence of various toxic agents causes disturbances in the structure and function of hepatocytes, leading to their damage and even death. Calcium ions enter the cell mostly through calcium channels, therefore, it has been suggested that calcium channel inhibitors (CCI) could protect hepatocytes from the action of toxic substances. The present study investigated the effect of the selected CCI (nifedipine, nitrendipine and verapamil) on liver function, measured by the efficiency of oxidation reaction, in this case by determination of the rate of antipyrine metabolism. The experiment was carried out using the method of extracorporeal liver perfusion (ELP). None of the studied CCI applied at a concentration of 50 micromol/l increased the rate of antipyrine metabolism over the whole period of ELP. However, supplementation of perfusion fluid with nifedipine, nitrendipine or verapamil at a concentration of 20 micromol/l considerably improved metabolic liver efficiency during the second hour of perfusion, i.e. at the time, when large number of hepatocytes started to perish, which could indicate protective action of the tested CCI. However, the CCI-induced acceleration of antipyrine metabolism was not a result of their influence on calcium channels, since these drugs block calcium channels, when given at the concentrations as high as 100-400 micromol/l. Moreover, it seems that facilitation of antipyrine metabolism during ELP was not due to their action on microsomal enzymes because CCI were administered at very low concentrations, besides, they are metabolic inhibitors, and not inducers. The present experiment suggests that low concentrations of CCI can exert hepatoprotective effect. However, confirmation of this conclusion requires further studies using other experimental methods.
由于各种毒性因子的影响，细胞质中钙离子浓度的增加会导致肝细胞结构和功能紊乱，进而造成肝细胞损伤甚至死亡。钙离子主要通过钙通道进入细胞，因此，有人提出钙通道抑制剂（CCI）可以保护肝细胞免受有毒物质的作用。本研究通过测定安替比林代谢速率来衡量氧化反应效率，从而研究了所选CCI（硝苯地平、尼群地平和维拉帕米）对肝功能的影响。实验采用体外肝脏灌注（ELP）方法进行。在ELP的整个过程中，以50微摩尔/升的浓度应用的所有研究的CCI均未提高安替比林的代谢速率。然而，在灌注液中添加浓度为20微摩尔/升的硝苯地平、尼群地平或维拉帕米，在灌注的第二个小时，即大量肝细胞开始死亡时，显著提高了肝脏代谢效率，这可能表明所测试的CCI具有保护作用。然而，CCI诱导的安替比林代谢加速并不是它们对钙通道产生影响的结果，因为这些药物在浓度高达100 - 400微摩尔/升时才会阻断钙通道。此外，ELP期间安替比林代谢的促进似乎不是由于它们对微粒体酶的作用，因为CCI是以非常低的浓度给药的，而且，它们是代谢抑制剂，而非诱导剂。本实验表明低浓度的CCI可发挥肝脏保护作用。然而，要证实这一结论还需要使用其他实验方法进行进一步研究。
