Kribben Bettina, Heller Jörg, Trebicka Jonel, Sauerbruch Tilman, Brüss Michael, Göthert Manfred, Molderings Gerhard J
Institute of Pharmacology and Toxicology, University of Bonn, Reuterstrasse 2B, 53113 Bonn, Germany.
Naunyn Schmiedebergs Arch Pharmacol. 2004 Feb;369(2):160-5. doi: 10.1007/s00210-003-0859-4. Epub 2004 Jan 15.
Agmatine interferes with polyamine metabolism and cell growth in cell culture. When absorbed from the gastrointestinal tract, it is accumulated in the liver. Based on these facts, the aim of the present study was to investigate the effects of agmatine on the proliferation of rat and human hepatoma cells and on regeneration of rat liver after partial two-thirds hepatectomy. In cultured cells of the rat and human hepatoma cell lines McRH7777 and HepG2 respectively, agmatine reduced ATP and protein contents (50% inhibition in the range of 169-569 microM) which were determined as estimates for the cell number. This antiproliferative action was not due to an effect on ornithine decarboxylase antizyme, since its intracellular concentration was not significantly changed by agmatine. In addition, agmatine metabolism by diamine oxidase seems not to be involved in the inhibition of cell growth and proliferation because the diamine oxidase inhibitor aminoguanidine did not alter agmatine's antiproliferative action. After two-thirds hepatectomy, daily administration of 250 mg and 500 mg agmatine to rats for 6 days by gavage reduced the weight gain of the remnant liver on day 7 by 19.5+/-0.9% and 22.3+/-1.5% respectively. The decrease in regeneration correlated with a pronounced accumulation of agmatine in the liver. Hence, the present data provide evidence of an involvement of agmatine in liver cell growth.
胍丁胺在细胞培养中会干扰多胺代谢和细胞生长。当它从胃肠道吸收后，会在肝脏中蓄积。基于这些事实，本研究的目的是探讨胍丁胺对大鼠和人肝癌细胞增殖以及大鼠三分之二肝部分切除术后肝脏再生的影响。在大鼠和人肝癌细胞系McRH7777和HepG2的培养细胞中，胍丁胺分别降低了ATP和蛋白质含量（在169 - 569微摩尔范围内抑制率达50%），这两项指标被用作细胞数量的估计值。这种抗增殖作用并非由于对鸟氨酸脱羧酶抗酶的影响，因为胍丁胺并未使其细胞内浓度发生显著变化。此外，二胺氧化酶对胍丁胺的代谢似乎与细胞生长和增殖的抑制无关，因为二胺氧化酶抑制剂氨基胍并未改变胍丁胺的抗增殖作用。在三分之二肝部分切除术后，通过灌胃每天给大鼠施用250毫克和500毫克胍丁胺，持续6天，结果在第7天时，残余肝脏的重量增加分别减少了19.5±0.9%和22.3±1.5%。再生的减少与肝脏中胍丁胺的显著蓄积相关。因此，目前的数据提供了胍丁胺参与肝细胞生长的证据。
