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表没食子儿茶素没食子酸酯对大鼠膀胱癌和乳腺癌的预防作用及其与血清和尿液中茶多酚水平的相关性

Preventive effects of polyphenon E on urinary bladder and mammary cancers in rats and correlations with serum and urine levels of tea polyphenols.

作者信息

Lubet Ronald A, Yang Chung S, Lee Mao-Jung, Hara Yukihiko, Kapetanovic Izet M, Crowell James A, Steele Vernon E, Juliana M Margaret, Grubbs Clinton J

机构信息

National Cancer Institute, Executive Plaza North, Suite 2110, 6130 Executive Boulevard, Bethesda, MD 20852, USA.

出版信息

Mol Cancer Ther. 2007 Jul;6(7):2022-8. doi: 10.1158/1535-7163.MCT-07-0058.

Abstract

Polyphenon E, a standardized mixture of green tea polyphenols, was examined for its chemopreventive efficacy against chemically induced urinary bladder and mammary cancers. In the present study, Polyphenon E was administered after the last dose of 4-hydroxybutyl(butyl)nitrosamine, or roughly 30% of the way into the experiment. Polyphenon E (100 or 250 mg/kg body weight/d) caused a dose-dependent decrease in palpable urinary bladder tumors [low dose, 14 of 34; high dose, 6 of 35; controls, 20 of 34 (P < 0.01)]. In the mammary cancer model, Polyphenon E [333 or 1,000 mg/kg body weight (BW)/d] was administered beginning 5 days after a single dose of methylnitrosourea. In contrast to its significant efficacy in bladder tumor prevention, Polyphenon E had a minimal effect in the prevention of mammary cancers. Levels of polyphenols were determined in the urine and serum of rats. Relatively high levels of various polyphenols (and metabolites) were found in the urine. However, virtually no epigallocatechin-3-gallate was observed in the urine because of low systemic bioavailability; although it represents almost 65% of the polyphenols in Polyphenon E. Levels of polyphenols in serum were 50 x to 1,000 x less than were observed in urine. The bioavailability of these tea polyphenols to different organ sites may contribute to the differing preventive efficacy of Polyphenon E against urinary bladder and mammary cancers.

摘要

绿茶多酚的标准化混合物表没食子儿茶素(Polyphenon E),针对化学诱导的膀胱癌和乳腺癌的化学预防功效进行了检测。在本研究中,表没食子儿茶素(Polyphenon E)在最后一剂4-羟基丁基(丁基)亚硝胺给药后,或大约在实验进行到30%的时候给药。表没食子儿茶素(Polyphenon E)(100或250毫克/千克体重/天)导致可触及的膀胱肿瘤出现剂量依赖性减少[低剂量组,34只中有14只;高剂量组,35只中有6只;对照组,34只中有20只(P<0.01)]。在乳腺癌模型中,表没食子儿茶素(Polyphenon E)[333或1000毫克/千克体重(BW)/天]在单剂量甲基亚硝基脲给药5天后开始给药。与它在预防膀胱肿瘤方面的显著功效形成对比的是,表没食子儿茶素(Polyphenon E)在预防乳腺癌方面作用极小。测定了大鼠尿液和血清中的多酚水平。在尿液中发现了相对较高水平的各种多酚(及其代谢物)。然而,由于全身生物利用度低,在尿液中几乎未观察到表没食子儿茶素-3-没食子酸酯;尽管它在表没食子儿茶素(Polyphenon E)中几乎占多酚的65%。血清中的多酚水平比尿液中观察到的低50倍至1000倍。这些茶多酚对不同器官部位的生物利用度可能导致表没食子儿茶素(Polyphenon E)对膀胱癌和乳腺癌的预防功效不同。

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