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槲皮素代谢产物对β-胡萝卜素增强苯并[a]芘暴露的A549细胞DNA损伤及细胞色素P1A1/2表达的影响。

Effects of quercetin metabolites on the enhancing effect of β-carotene on DNA damage and cytochrome P1A1/2 expression in benzo[a]pyrene-exposed A549 cells.

作者信息

Chang Yan-Zin, Lin Hsiao-Chun, Chan Shu-Ting, Yeh Shu-Lan

机构信息

Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan, ROC.

Department of Nutritional Science, Chung Shan Medical University, Taichung, Taiwan, ROC.

出版信息

Food Chem. 2012 Jul 15;133(2):445-50. doi: 10.1016/j.foodchem.2012.01.060. Epub 2012 Jan 27.

DOI:10.1016/j.foodchem.2012.01.060
PMID:25683418
Abstract

A549 cells were pre-incubated with β-carotene (BC) alone or in combination with quercetin or three major quercetin metabolites in human plasma, quercetin 3-glucuronide (Q3G), quercetin 3'-sulphate (Q3'S) and isorhamnetin, followed by incubation with benzo[a]pyrene (BaP), to investigate the effects of these compounds on the BaP-induced harmful effects of BC. All the quercetin metabolites at 10μM inhibited BaP+BC-induced cell death. Q3'S, Q3G and isorhamnetin also significantly decreased BaP±BC-induced DNA damage by 64%, 60% and 24%, respectively. In a similar order, these compounds suppressed BaP+BC-induced cytochrome P450 (CYP)1A1/1A2 expression by 10-50%. Q3G and Q3'S significantly decreased the intracellular reactive oxygen species formation induced by BaP+BC; however, Q3G had the best effect on decreasing the loss of BC induced by Fe/NTA. The combined effects of quercetin metabolites were additive. This study indicates that quercetin metabolites decrease the BaP-induced harmful effect of β-carotene in A549 cells by downregulating the expression of CYP1A1/1A2, at least in part.

摘要

将A549细胞单独用β-胡萝卜素(BC)预处理,或与槲皮素或人血浆中的三种主要槲皮素代谢物(槲皮素3-葡萄糖醛酸苷(Q3G)、槲皮素3'-硫酸盐(Q3'S)和异鼠李素)联合预处理,然后与苯并[a]芘(BaP)共同孵育,以研究这些化合物对BaP诱导的BC有害作用的影响。所有浓度为10μM的槲皮素代谢物均抑制BaP+BC诱导的细胞死亡。Q3'S、Q3G和异鼠李素还分别使BaP±BC诱导的DNA损伤显著降低64%、60%和24%。按相似顺序,这些化合物使BaP+BC诱导的细胞色素P450(CYP)1A1/1A2表达下调10%-50%。Q3G和Q3'S显著降低了BaP+BC诱导的细胞内活性氧的形成;然而,Q3G在减少Fe/NTA诱导的BC损失方面效果最佳。槲皮素代谢物的联合作用具有相加性。本研究表明,槲皮素代谢物至少部分地通过下调CYP1A1/1A2的表达来降低BaP诱导的β-胡萝卜素在A549细胞中的有害作用。

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