Red wine polyphenols influence carcinogenesis, intestinal microflora, oxidative damage and gene expression profiles of colonic mucosa in F344 rats
Red wine polyphenols influence carcinogenesis, intestinal microflora, oxidative damage and gene expression profiles of colonic mucosa in F344 rats
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DOI：
10.1016/j.mrfmmm.2005.04.022
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发表时间：
2005-12-11
影响因子：
2.3
通讯作者：
Cresci, A
中科院分区：
文献类型：
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作者：
Dolara, P;Luceri, C;Cresci, A
茶和红酒等其他饮料中的多酚被认为是可能的癌症化学预防剂。在这里，我们报告的红葡萄酒多酚（50毫克/公斤）的饮食给F344大鼠16周抑制氧化偶氮甲烷（AOM，7.4毫克/公斤，总剂量74毫克/公斤）或二甲基肼（DMH，30毫克/公斤，总剂量，300毫克/公斤）诱导的结肠癌。与对照组相比，多酚处理的动物具有一贯较低的肿瘤产量。在多酚处理的大鼠中，处死时粪便中的主要细菌菌株为拟杆菌属、乳杆菌属和双歧杆菌属，而在对照喂养的大鼠中主要鉴定的微生物是拟杆菌属、梭菌属和丙酸杆菌属。葡萄酒多酚（57 mg/kg，10天，通过管饲法）给药于未用致癌物处理的大鼠，如彗星试验所测量的，产生结肠粘膜的DNA氧化损伤的基础水平的显著降低（平均嘧啶氧化降低62%，嘌呤氧化降低57%，p < 0.05）。为了进一步探索葡萄酒多酚的分子效应，我们使用微阵列技术研究基因表达谱：大鼠用50 mg/kg葡萄酒多酚处理14天，混合在饮食中。对5707个基因的全局表达分析揭示了参与广泛生理功能的基因的广泛下调，如代谢、运输、信号转导和细胞间信号传导。通过分析代谢途径与GenMAPP软件程序，我们观察到两个主要的调节途径下调多酚治疗大鼠的结肠粘膜：炎症反应和类固醇代谢。我们还发现许多调节细胞表面抗原、代谢酶和细胞对氧化应激反应的基因下调。总之，氧化损伤的减少，结肠植物群的调制和基因表达的变化可能都与葡萄酒多酚对肠道功能和致癌作用的调制一致。(c)2005年由Elsevier B. V.出版
Polyphenols from tea and other beverages such as red wine have been regarded with interest as possible chemopreventive agents against cancer. Here we report that red wine polyphenols (50 mg/kg) administered with the diet to F344 rats for 16 weeks inhibited colon carcinogenesis induced by azoxymethane (AOM, 7.4 mg/kg, total dose 74 mg/kg) or dimethylhydrazine (DMH, 30 mg/kg, total dose, 300 mg/kg). Polyphenol-treated animals had a consistently lower tumour yield compared to controls. In polyphenol-treated rats, the main bacterial strains in the faeces at sacrifice were Bacteroides, Lactobacillus and Bifidobacterium spp., whereas microorganisms predominantly identified in control-fed rats were Bacteroides, Clostridium and Propionibacterium spp. Wine polyphenols (57 mg/kg for 10 days, by gavage), administered to rats not treated with carcinogens, produced a significant decrease in the basal level of DNA oxidative damage of the colon mucosa as measured with the comet assay (average pyrimidine oxidation was reduced by 62% and purine oxidation by 57%, p < 0.05). To further explore the molecular effects of wine polyphenols we used the microarray technology to study gene expression profiles: rats were treated with 50 mg/kg wine polyphenols for 14 days, mixed in the diet. Global expression analysis of 5707 genes revealed an extensive down-regulation of genes involved in a wide range of physiological functions, such as metabolism, transport, signal transduction and intercellular signalling. By analysing metabolic pathways with the GenMAPP software program we observed that two major regulatory pathways were down-regulated in the colon mucosa of polyphenols-treated rats: inflammatory response and steroid metabolism. We also found a down-regulation of many genes regulating cell surface antigens, metabolic enzymes and cellular response to oxidative stress. In conclusion, reduction of oxidative damage, modulation of colonic flora and variation in gene expression may all concur in the modulation of intestinal function and carcinogenesis by wine polyphenols. (c) 2005 Published by Elsevier B.V.