EFFECT OF ELLAGIC ACID ON HEPATIC AND PULMONARY XENOBIOTIC METABOLISM IN MICE - STUDIES ON THE MECHANISM OF ITS ANTICARCINOGENIC ACTION
EFFECT OF ELLAGIC ACID ON HEPATIC AND PULMONARY XENOBIOTIC METABOLISM IN MICE - STUDIES ON THE MECHANISM OF ITS ANTICARCINOGENIC ACTION
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DOI：
10.1093/carcin/6.10.1409
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发表时间：
1985-01-01
期刊：
影响因子：
4.7
通讯作者：
MUKHTAR, H
中科院分区：
文献类型：
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作者：
DAS, M;BICKERS, DR;MUKHTAR, H
我们最近的研究表明，鞣花酸是一种天然的饮食植物苯酚，可以保护BALB/c小鼠免受3-甲基胆蒽诱导的皮肤肿瘤的影响。为进一步阐明鞣花酸的抗肿瘤作用机制，研究了其对小鼠肝、肺苯并[a]芘(BP)代谢、细胞色素P450依赖的单加氧酶和谷胱甘肽S转移酶活性的影响。慢性口服该化合物(0.3 mg/L，连续16周)或急性腹腔注射(50 mg/kg，连续5天)，可使肝、肺细胞色素P-450水平下降20-25%。两组动物的肝脏和肺芳烃羟基酶和7-乙氧基香豆素O-脱乙基酶活性分别比各自的非鞣花酸处理对照组低33-52%和28-43%。两组小鼠肝、肺氨基比林N-脱甲基酶和环氧化物水解酶活性均无明显变化。以BP-4，5-氧化物或1-氯-2，4-二硝基苯为底物的肝脏谷胱甘肽S转移酶活性在两组动物中分别提高51-79%和38-58%。H.P.L.C.通过肝和肺微粒体对BP有机溶剂可溶代谢产物的分析表明，BP对二醇的形成(包括BP-7，8-二醇)以及酚类和苯二酚都有抑制作用。在肝脏中，口服给药后的这些抑制作用比腹腔给药后更明显。结果表明，急性和慢性给药均可抑制血压代谢和/或增强谷胱甘肽S转移酶活性。因此，鞣花酸对多环芳烃代谢的调节可能与该化合物的抗癌作用有关。
Our recent studies have shown that ellagic acid, a naturally occurring dietary plant phenol, protects BALB/c mice against 3-methylcholanthrene-induced skin tumorigenesis. To further elucidate the mechanism of the antineoplastic action of ellagic acid its effect on hepatic and pulmonary benzo[a]pyrene (BP) metaboism, cytochrome P-450-dependent monooxygenases and glutathione S-transferase activities were studied in BALB/c mice. Chronic oral feeding of the compound in drinking water (0.3 mg/l for 16 weeks) or acute intraperitoneal administration (50 mg/kg for five consecutive days) of ellagic acid resulted in 20-25% decreases in hepatic and pulmonary cytochrome P-450 levels. Hepatic and pulmonary aryl hydrocarbon hydroxylase and 7-ethoxycoumarin O-deethylase activities in both groups of ellagic acid-treated animals were 33-52% and 28-43% lower than their respective non-ellagic acid-treatment controls. Hepatic as well as pulmonary aminopyrine N-demethylase and epoxide hydrolase activities were unchanged in both groups of ellagic acid-treated mice. Hepatic glutathione S-transferase activity towards BP-4,5-oxide or 1-chloro-2,4-dinitrobenzene as substrates was found to be enhanced 51-79% and 38-58% in both groups of animals. H.p.l.c. analysis of organic solvent-soluble metabolites of BP by liver and lung microsomes indicated a subdstantial inhibition of diol formation (including BP-7,8-diol), as well as of phenols and quinones. In liver, these inhibitory effects were more pronounced after oral feeding than after intraperitoneal adminstration. Our results indicate that both acute and chronic administration of ellagic acid inhibits BP metabolism and/or enhances glutathione S-transferase activity. Thus the modulation of polycyclic aromatic hydrocarbon metabolism by ellagic acid may be related to the anticarcinogenic effects of this compound.