Influence of cimetidine and its metabolites on Cisplatin-Investigation of adduct formation by means of electrochemistry/liquid chromatography/electrospray mass spectrometry
Influence of cimetidine and its metabolites on Cisplatin-Investigation of adduct formation by means of electrochemistry/liquid chromatography/electrospray mass spectrometry
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DOI：
10.1016/j.chroma.2012.12.069
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发表时间：
2013-03-01
影响因子：
4.1
通讯作者：
Karst, Uwe
中科院分区：
文献类型：
--
作者：
Brauckmann, Christine;Faber, Helene;Karst, Uwe
西咪替丁已被研究作为癌症化疗的添加剂。据称它可以减少顺铂的副作用。本研究的重点是顺铂和西咪替丁在分子水平上可能的相互作用。由于西咪替丁在肝脏中代谢，其代谢物与顺铂之间的相互作用也被研究。采用LC/ESI-MS对顺铂-西咪替丁加合物进行检测。第二步，采用电化学氧化法模拟西咪替丁的代谢。这些结果与西咪替丁用大鼠和人肝细胞微粒体孵育的结果进行了比较。由于两种方法显示出相关性，因此进一步采用电化学方法研究顺铂与西咪替丁代谢物的相互作用。然而，对于纯西咪替丁及其代谢物，可能在人体内发生的显著相互作用既不能观察到。最后，利用模型蛋白p-乳球蛋白a研究了西咪替丁对顺铂-蛋白相互作用的影响。在西咪替丁存在的情况下，顺铂对模型蛋白的亲和力似乎增加了。(C) 2013 Elsevier B.V.版权所有
Cimetidine has been studied as an additive in cancer chemotherapy. It is claimed to reduce the side effects of Cisplatin. This study focuses on possible interactions between Cisplatin and cimetidine on the molecular level. Due to the fact that cimetidine is metabolized in the liver, interactions between its metabolites and Cisplatin are also investigated. By means of LC/ESI-MS, Cisplatin-cimetidine adducts were detected. In a second step, the metabolism of cimetidine was simulated by electrochemical oxidation. These results were compared with microsomal incubations of cimetidine using rat and human liver cell microsomes. Because the two methods showed a correlation, the electrochemical approach was further used to investigate Cisplatin's interactions with metabolites of cimetidine. However, notable interactions that might take place in the human body could neither be observed for pure cimetidine nor for its metabolites. Finally, the impact of cimetidine on Cisplatin-protein interactions were studied using the model protein p-lactoglobulin A. In the presence of cimetidine, the affinity of Cisplatin towards the model protein appears to be increased. (C) 2013 Elsevier B.V. All rights reserved.