Alcohol hinders the Anti-Carcinogenic effect of Resveratrol in the Colon of rats

Everton Félix Cesar, S. B. Minto, S. Garcia
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Abstract

Resveratrol (RESV), a polyphenol present in wine and other natural sources, has potent anti-oxidant and chemopreventive effect against various types of cancer by multiple mechanisms of action. On the other hand, ethanol, which is also one important component of wine, is associated with increased oxidative stress and risk of cancer in general, including the colonic cancer. It is unknown whether the anti-oxidant and anti-carcinogenic effects of RESV could be counterbalanced by alcohol in vivo. Thus, the present study evaluated the anti-neoplastic action of RESV, pure or associated with ethanol on the colon carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in rats. It was performed a detailed analysis of aberrant crypt foci (ACF) formation and the systemic oxidative stress through malondialdehyde (MDA) dosage. The inflammatory process, which is associated to the colonic carcinogenesis, was estimated by the immune-expression of cyclooxigenase-2 (COX-2). Our experiments were performed in 32 wistar rats, divided into four groups: the group C was the control, the group M received MNNG (5mg/ml), the group MR received MNNG and RESV (1mg/kg/day) and the group MRA received RESV and alcohol (0,377g/kg/day). As a result, RESV decreased the number of ACF and COX-2 expression, but these effects were abolished by the alcohol. RESV reduced the production of MDA in all treated groups, evidencing that its systemic antioxidant effect was also present in the animals treated with alcohol. It was concluded that alcohol hindered the anti-carcinogenic effects of RESV. This effect of alcohol should be attributed to its pro-inflammatory effects, which have avoided the anti-inflammatory properties of RESV.
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白藜芦醇(RESV)是一种存在于葡萄酒和其他天然来源中的多酚,通过多种机制对多种类型的癌症具有强大的抗氧化和化学预防作用。另一方面,乙醇也是葡萄酒的重要成分之一,它与氧化应激增加和患癌症的风险有关,包括结肠癌。RESV的抗氧化和抗癌作用是否能在体内被酒精抵消尚不清楚。因此,本研究评估了RESV,纯RESV或与乙醇联合RESV对n -甲基-n '-硝基-n -亚硝基胍(MNNG)诱导的大鼠结肠癌的抗肿瘤作用。通过丙二醛(MDA)剂量对异常隐窝灶(ACF)形成和全身氧化应激的影响进行了详细分析。通过环氧化酶-2 (COX-2)的免疫表达来估计与结肠癌发生相关的炎症过程。实验选用32只wistar大鼠,分为4组:C组为对照组,M组给予MNNG (5mg/ml), MR组给予MNNG + RESV (1mg/kg/day), MRA组给予RESV +酒精(0,377g/kg/day)。结果,RESV降低了ACF和COX-2的表达量,但这些作用被酒精消除。RESV降低了所有治疗组中MDA的生成,证明其系统性抗氧化作用也存在于酒精治疗的动物中。由此可见,酒精阻碍了RESV的抗癌作用。酒精的这种作用应该归因于它的促炎作用,这避免了RESV的抗炎特性。
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