Cavin C, Marin-Kuan M, Langouët S, Bezençon C, Guignard G, Verguet C, Piguet D, Holzhäuser D, Cornaz R, Schilter B
Quality and Safety Department, Nestlé Research Center, PO Box 44, Vers-chez-les-Blanc, CH-1000 Lausanne 26, Switzerland.
Food Chem Toxicol. 2008 Apr;46(4):1239-48. doi: 10.1016/j.fct.2007.09.099. Epub 2007 Sep 26.
Coffee consumption has been associated with a significant decrease in the risk of developing chronic diseases such as Parkinson disease, diabetes type-2 and several types of cancers (e.g. colon, liver). In the present study, a coffee-dependent induction of enzymes involved in xenobiotic detoxification processes was observed in rat liver and primary hepatocytes. In addition, coffee was found to induce the mRNA and protein expression of enzymes involved in cellular antioxidant defenses. These inductions were correlated with the activation of the Nrf2 transcription factor as shown using an ARE-reporter luciferase assay. The induction of detoxifying enzymes GSTs and AKR is compatible with a protection against both genotoxicity and cytotoxicity of aflatoxin B1 (AFB1). This hypothesis was confirmed in in vitro and ex vivo test systems, where coffee reduced both AFB1-DNA and protein adducts. Interestingly, coffee was also found to inhibit cytochrome CYP1A1/2, indicating that other mechanisms different from a stimulation of detoxification may also play a significant role in the chemoprotective effects of coffee. Further investigations in either human liver cell line and primary hepatocytes indicated that the chemoprotective effects of coffee against AFB1 genotoxicity are likely to be of relevance for humans. These data strongly suggest that coffee may protect against the adverse effects of AFB1. In addition, the coffee-mediated stimulation of the Nrf2-ARE pathway resulting in increased endogenous defense mechanisms against electrophilic but also oxidative insults further support that coffee may be associated with a protection against various types of chemical stresses.
咖啡消费与患帕金森病、2型糖尿病和几种癌症（如结肠癌、肝癌）等慢性疾病风险的显著降低有关。在本研究中，在大鼠肝脏和原代肝细胞中观察到咖啡依赖性诱导参与外源性解毒过程的酶。此外，发现咖啡可诱导参与细胞抗氧化防御的酶的mRNA和蛋白质表达。如使用ARE报告荧光素酶测定法所示，这些诱导与Nrf2转录因子的激活相关。解毒酶GSTs和AKR的诱导与针对黄曲霉毒素B1（AFB1）的基因毒性和细胞毒性的保护作用相一致。这一假设在体外和离体测试系统中得到证实，其中咖啡减少了AFB1-DNA和蛋白质加合物。有趣的是，还发现咖啡抑制细胞色素CYP1A1/2，这表明与刺激解毒不同的其他机制也可能在咖啡的化学保护作用中发挥重要作用。在人肝细胞系和原代肝细胞中的进一步研究表明，咖啡对AFB1基因毒性的化学保护作用可能与人类相关。这些数据强烈表明咖啡可能预防AFB1的不良影响。此外，咖啡介导的Nrf2-ARE途径的刺激导致针对亲电以及氧化损伤的内源性防御机制增加，进一步支持咖啡可能与针对各种类型化学应激的保护作用相关。
