Enhancement of the chemoprotective enzymes glucuronosyl transferase and glutathione transferase in specific organs of the rat by the coffee components kahweol and cafestol
Enhancement of the chemoprotective enzymes glucuronosyl transferase and glutathione transferase in specific organs of the rat by the coffee components kahweol and cafestol
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DOI：
10.1007/s00204-002-0322-1
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发表时间：
2002-05-01
影响因子：
6.1
通讯作者：
Schulte-Hermann, R
中科院分区：
文献类型：
--
作者：
Huber, WW;Prustomersky, S;Schulte-Hermann, R
据报道，咖啡组分咖啡醇和咖啡豆醇（K/C）可保护大鼠结肠和其他器官免受2-氨基-1-甲基-6-苯基咪唑[4，5-B]吡啶（PhIP）和黄曲霉毒素B1形成的DNA加合物的影响。PhIP是一种熟食致突变剂，人类大量接触该物质并在结肠癌病因学中发挥作用，有趣的是，这种癌症似乎在高K/C含量的咖啡消费者中以较低的速度发展。早期在啮齿动物肝脏中的研究表明，K/C的化学预防作用中的关键作用可能是由于这些化合物通过谷胱甘肽转移酶（GST）诱导外源性物质解毒并增强相应辅因子谷胱甘肽的合成的潜力。然而，PhIP等诱变剂也可通过UDP-葡萄糖醛酸基转移酶（UDPGT）解毒，但缺乏关于K/C潜在影响的数据。因此，在本研究中，我们研究了K/C对UDPGT的影响，同时，我们研究了整体GST和个别GST类的模式，特别是GST-θ，这是不包括在早期的实验。此外，我们分析了这些潜在的化学预防作用的器官依赖性。以0.122%的K/C在饲料中饲喂雄性F344大鼠10天。使用5种特征底物定量肝脏、肾脏、肺、结肠、唾液腺、胰腺、睾丸、心脏和脾脏中的酶活性，并使用亲和色谱/HPLC研究GST类α、μ和pi的肝脏蛋白模式。我们的研究表明，K/C不仅能够增加总体GST和GST类α、μ和pi，而且还能够增强UDGPT和GST-θ。所有研究的K/C效应在肝脏和肾脏中最强，在肺和结肠中观察到一些反应，但在其他器官中没有反应。总之，我们的研究结果表明，K/C处理导致第11阶段解毒酶的广谱增加。值得注意的是，这些作用优先发生在灌注良好的器官肝脏和肾脏中，因此这不仅有助于局部保护，而且有助于远处刺激较少的器官如结肠中的抗癌作用。
The coffee components kahweol and cafestol (K/C) have been reported to protect the colon and other organs of the rat against the formation of DNA adducts by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and aflatoxin B1. PhIP is a cooked-food mutagen to which significant human exposure and a role in colon cancer etiology are attributed, and, interestingly, such cancers appear to develop at a lower rate in consumers of coffees with high amounts of K/C. Earlier studies in rodent liver have shown that a key role in the chemopreventive effect of K/C is likely to be due to the potential of these compounds to induce the detoxification of xenobiotics by glutathione transferase (GST) and to enhance the synthesis of the corresponding co-factor glutathione. However, mutagens like PhIP may also be detoxified by UDP-glucuronosyl transferase (UDPGT) for which data are lacking regarding a potential effect of K/C. Therefore, in the present study, we investigated the effect of K/C on UDPGT and, concomitantly, we studied overall GST and the pattern of individual GST classes, particularly GST-theta, which was not included in earlier experiments. In addition, we analyzed the organ-dependence of these potentially chemopreventive effects. K/C was fed to male F344 rats at 0.122% in the chow for 10 days. Enzyme activities in liver, kidney, lung, colon, salivary gland, pancreas, testis, heart and spleen were quantified using five characteristic substrates and the hepatic protein pattern of GST classes alpha, mu, and pi was studied with affinity chromatography/HPLC. Our study showed that K/C is not only capable of increasing overall GST and GST classes alpha, mu, and pi but also of enhancing UDGPT and GST-theta. All investigated K/C effects were strongest in liver and kidney, and some response was seen in lung and colon but none in the other organs. In summary, our results show that K/C treatment leads to a wide spectrum of increases in phase 11 detoxification enzymes. Notably, these effects occurred preferentially in the well perfused organs liver and kidney, which may thus not only contribute to local protection but also to anti-carcinogenesis in distant, less stimulated organs such as the colon.