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黄酮类化合物化学预防的作用机制。

Mechanisms involved in the chemoprevention of flavonoids.

作者信息

Siess M H, Le Bon A M, Canivenc-Lavier M C, Suschetet M

机构信息

Unité de Toxicologie Nutritionnelle, Institut National de la Recherche Agronomique, Dijon, France.

出版信息

Biofactors. 2000;12(1-4):193-9. doi: 10.1002/biof.5520120131.

DOI:10.1002/biof.5520120131
PMID:11216486
Abstract

Flavonoids, widespread in edible plants, have been studied extensively for their anticarcinogenic properties. However, only few studies have been done with these constituents being administered by the dietary route. In our research, the effects of feeding rats with flavone, flavanone, tangeretin, and quercetin were investigated on two steps of aflatoxin B1 (AFB1)-induced hepatocarcinogenesis (initiation and promotion). Nonpolar flavonoids such as flavone, flavanone and tangeretin administered through the initiation period, decreased the number of -gamma-glutamyl transpeptidase-preneoplastic foci. In the same conditions of administration, quercetin, a polyhydroxylated flavonoid, showed no protective effect. Moreover, feeding rats with flavanone during the phenobarbital-induced promotion step significantly reduced the areas of placental glutathione S-transferase preneoplastic foci. Quercetin, flavone, and tangeretin, administered in the same conditions, caused no significant effect. Therefore flavanone act as an anti-initiator as well as an anti-promotor. Several mechanisms were involved in the anti-initiating effects of flavone, flavanone, and tangeretin: enhancement of enzymes involved in the detoxication of AFB1 (glutathione S-transferase, UDP-glucuronyl transferase), increase of the formation of AFB1-glutathione conjugates and inhibition of the binding of AFB1 to DNA. Although the relevance of these data to the human situation remains to be demonstrated, they confirm that several flavonoids administered by the dietary route possess promising chemoprotective effects.

摘要

黄酮类化合物广泛存在于可食用植物中,因其抗癌特性而受到广泛研究。然而,关于通过饮食途径摄入这些成分的研究却很少。在我们的研究中,研究了给大鼠喂食黄酮、黄烷酮、橘皮素和槲皮素对黄曲霉毒素B1(AFB1)诱导的肝癌发生的两个阶段(启动和促进)的影响。在启动期给予非极性黄酮类化合物,如黄酮、黄烷酮和橘皮素,可减少γ-谷氨酰转肽酶前肿瘤灶的数量。在相同的给药条件下,多羟基黄酮槲皮素没有显示出保护作用。此外,在苯巴比妥诱导的促进阶段给大鼠喂食黄烷酮,可显著减少胎盘谷胱甘肽S-转移酶前肿瘤灶的面积。在相同条件下给予槲皮素、黄酮和橘皮素,没有产生显著影响。因此,黄烷酮既可以作为抗启动剂,也可以作为抗促进剂。黄酮、黄烷酮和橘皮素的抗启动作用涉及多种机制:增强参与AFB1解毒的酶(谷胱甘肽S-转移酶、UDP-葡萄糖醛酸基转移酶),增加AFB1-谷胱甘肽共轭物的形成,并抑制AFB1与DNA的结合。尽管这些数据与人类情况的相关性仍有待证明,但它们证实了通过饮食途径摄入的几种黄酮类化合物具有有前景的化学保护作用。

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