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茶饮料对醛氧化酶活性的影响。

Effect of tea beverages on aldehyde oxidase activity.

机构信息

Faculty of Pharmaceutical Science, Hiroshima International University, Hiroshima, Japan.

出版信息

Drug Metab Pharmacokinet. 2011;26(1):94-101. doi: 10.2133/dmpk.dmpk-10-nt-078. Epub 2010 Nov 12.

Abstract

Aldehyde oxidase (AO) plays an important role in metabolizing antitumor and antiviral drugs, including methotrexate, cyclophosphamide and acyclovir. Green tea and its catechins have been shown to modulate the activities of various xenobiotic-metabolizing cytochrome P450 species, both in vivo and in vitro, but their effect on AO has not been studied. Therefore, we evaluated the effect of tea beverages on AO activity in rat and human liver cytosol. We also investigated the influence of several catechins on AO activity in rat liver cytosol. AO activity was evaluated in terms of oxidation of N-1-methylnicotinamide to N-1-methyl-2-pyridone-5-carboxamide and N-1-methyl-4-pyridone-3-carboxamide. Bottled green tea beverages at 10% (vol/vol) inhibited AO activity by 90.0-93.5%, while at 1.0% (vol/vol), they reduced AO activity by 73.9-90.0%. At 0.1% (vol/vol), green tea II and III, which have high contents of catechins and their derivatives, inhibited AO activity by 24.3% and 38.8%, respectively. Bottled mineral water had no effect. AO activity was inhibited potently by epicatechin and epicatechin gallate. These results indicate that the AO-inhibitory activity of tea beverages is predominantly due to catechins and their derivatives. Thus, consumption of tea beverages may cause a decrease of AO activity, which may result in reduced clearance of drugs that are AO substrates.

摘要

醛氧化酶(AO)在代谢抗肿瘤和抗病毒药物方面发挥着重要作用,包括甲氨蝶呤、环磷酰胺和阿昔洛韦。研究表明,绿茶及其儿茶素可以调节各种异源生物代谢细胞色素 P450 种类的活性,无论是在体内还是体外,但它们对 AO 的影响尚未得到研究。因此,我们评估了茶饮料对大鼠和人肝胞浆中 AO 活性的影响。我们还研究了几种儿茶素对大鼠肝胞浆中 AO 活性的影响。AO 活性是通过 N-1-甲基烟酰胺氧化为 N-1-甲基-2-吡啶酮-5-羧酰胺和 N-1-甲基-4-吡啶酮-3-羧酰胺来评估的。10%(体积/体积)的瓶装绿茶饮料抑制 AO 活性 90.0-93.5%,而 1.0%(体积/体积)时抑制 AO 活性 73.9-90.0%。在 0.1%(体积/体积)时,儿茶素和其衍生物含量较高的绿茶 II 和 III 分别抑制 AO 活性 24.3%和 38.8%。瓶装矿泉水没有效果。表儿茶素和表儿茶素没食子酸酯强烈抑制 AO 活性。这些结果表明,茶饮料的 AO 抑制活性主要归因于儿茶素及其衍生物。因此,茶饮料的消耗可能会导致 AO 活性降低,从而导致 AO 底物药物的清除减少。

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