The effects of selected flavonoids on cytochromes P450 in rat liver and small intestine.
The effects of selected flavonoids on cytochromes P450 in rat liver and small intestine.
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DOI：
10.2478/v10102-009-0018-y
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发表时间：
2009-09
影响因子：
--
通讯作者：
Hodek P
中科院分区：
文献类型：
--
作者：
Křížková J;Burdová K;Stiborová M;Křen V;Hodek P
近年来，含有浓缩植物化学物质（如类黄酮）的膳食补充剂的消费和使用急剧增加。黄酮类化合物作为外源性化合物，具有调节细胞色素P450（CYPs）活性的潜力，CYPs是参与食品和环境致癌物活化和解毒的外源性代谢酶。因此，本研究的目的是研究模型糖基化和去糖基化黄酮对大鼠肝脏和小肠CYP的影响，这两个主要器官负责异生物质代谢，p.o.通过灌胃给药。采用Western印迹技术和烷基试卤灵衍生物的比活性测定法测定了两种糖基化黄酮类化合物（异槲皮苷、芦丁）及其苷元（槲皮素）对CYP的影响。在肝微粒体中，只有在异槲皮苷处理后才观察到所有测量的标记物活性（EROD，MROD，PROD）的显著增加。为了评价黄酮类化合物对沿着小肠CYP的影响，将组织解剖成近端（靠近幽门）、中间和远端部分。在所有供试化合物中，异槲皮苷是最有效的促排剂，即在小肠中部。所获得的数据证明了黄酮苷和苷元对大鼠肝脏和小肠中的RP1表达的不同影响。由于这些植物化学物质是外源性物质，因此它们会增加人类患癌症的风险，因此应仔细考虑大量食用。
In recent years, the consumption and use of dietary supplements containing concentrated phytochemicals (e.g. flavonoids) increased dramatically. Flavonoids, as foreign compounds (xenobiotics), have great potential to modulate the activity of cytochrome P450s (CYPs), xenobiotic-metabolizing enzymes involved in the activation and detoxification of food and environmental carcinogens. Thus, the aim of this study was to investigate the effects of model glycosylated and deglycosylated flavonoids on CYPs in rat liver and small intestine, as the two main organs responsible for xenobiotic metabolism, after p.o. administration by gastric gavages. The effects of two glycosylated flavonoids (isoquercitrin, rutin) and their aglycone (quercetin) on CYPs were determined using Western blotting technique and specific activity assays with alkyl-resorufin derivatives. In liver microsomes, a considerable increase of all the measured marker activities (EROD, MROD, PROD) was observed only after isoquercitrin treatment. To evaluate the effects of flavonoids on CYPs along small intestine, the tissue was dissected into proximal (near pylorus), middle and distal parts. Of all the tested compounds, isoquercitrin was the most efficient CYP inducer, namely in the middle part of small intestine. Obtained data demonstrate the different effects of flavonoid glycosides and aglycone on CYP expression in rat liver and small intestine. Since these phytochemicals are xenobiotics, and thus they can increase the human risk of cancer development, their consumption in large quantities should be carefully considered.