Dolara Piero, Luceri Cristina, De Filippo Carlotta, Femia Angelo Pietro, Giovannelli Lisa, Caderni Giovanna, Cecchini Cinzia, Silvi Stefania, Orpianesi Carla, Cresci Alberto
Department of Pharmacology, University of Florence, Viale G. Pieraccini 6, 50139 Florence, Italy.
Mutat Res. 2005 Dec 11;591(1-2):237-46. doi: 10.1016/j.mrfmmm.2005.04.022. Epub 2005 Nov 15.
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.
来自茶和其他饮品（如红酒）中的多酚类物质，作为可能的抗癌化学预防剂受到了关注。在此我们报告，给F344大鼠喂食含50毫克/千克红酒多酚的食物，持续16周，可抑制由氧化偶氮甲烷（AOM，7.4毫克/千克，总剂量74毫克/千克）或二甲基肼（DMH，30毫克/千克，总剂量300毫克/千克）诱导的结肠癌发生。与对照组相比，多酚处理组动物的肿瘤发生率持续较低。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、乳酸杆菌属和双歧杆菌属，而在对照喂养大鼠中主要鉴定出的微生物为拟杆菌属、梭菌属和丙酸杆菌属。给未用致癌物处理的大鼠灌胃57毫克/千克的红酒多酚，持续10天，用彗星试验检测发现，结肠黏膜DNA氧化损伤的基础水平显著降低（平均嘧啶氧化减少62%，嘌呤氧化减少57%，p<0.05）。为进一步探究红酒多酚的分子效应，我们使用微阵列技术研究基因表达谱：大鼠喂食含50毫克/千克红酒多酚的食物，持续14天。对5707个基因的整体表达分析显示，参与广泛生理功能（如代谢、转运、信号转导和细胞间信号传导）的基因大量下调。通过使用GenMAPP软件程序分析代谢途径，我们观察到在多酚处理大鼠的结肠黏膜中，两条主要调节途径下调：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、结肠菌群的调节以及基因表达的变化，都可能共同参与红酒多酚对肠道功能和癌症发生的调节作用。
