INCREASE OF NAD(P)H-QUINONE REDUCTASE BY DIETARY ANTIOXIDANTS - POSSIBLE ROLE IN PROTECTION AGAINST CARCINOGENESIS AND TOXICITY
INCREASE OF NAD(P)H-QUINONE REDUCTASE BY DIETARY ANTIOXIDANTS - POSSIBLE ROLE IN PROTECTION AGAINST CARCINOGENESIS AND TOXICITY
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DOI：
10.1073/pnas.77.9.5216
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发表时间：
1980-01-01
期刊：
影响因子：
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通讯作者：
TALALAY, P
中科院分区：
文献类型：
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作者：
BENSON, AM;HUNKELER, MJ;TALALAY, P
2(3)-叔丁基-4-羟基茴香醚（BHA）是一种广泛使用的抗氧化食品添加剂，可以防止化学致癌和毒性。本报告是关于增强双酚醇抑制NAD(P)H：醌还原酶[NAD(P)H脱氢酶（醌）；NAD（P)H:（醌受体）氧化还原酶，EC 1.6.99.2）在小鼠组织中的活性对饮食中给予BHA的反应。在bha喂养小鼠的15个组织中，有10个组织的胞质醌还原酶特异性活性显著增加。在肝脏中观察到最大比例的增加，达到对照水平的10倍。BHA还能使肾、肺和上小肠粘膜的醌还原酶活性提高数倍。肝脏和消化组织醌还原酶活性的增加与先前观察到的谷胱甘肽s转移酶（EC 2.5.1.18）和环氧化物水合酶（EC 3.3.2.3）活性的增加相当。醌类化合物是芳烃氧化代谢的有毒产物之一。NAD(P)H：醌还原酶对结构多样的疏水醌具有广泛的特异性，并可能促进醌的微粒体代谢为易于排泄的偶联物。BHA的保护作用似乎至少部分是由于这种抗氧化剂能够增加啮齿动物组织中几种酶的活性，这些酶参与了各种异种生物的非氧化代谢。
2(3)-tert-Butyl-4-hydroxyanisole (BHA) is a widely used antioxidant food additive that protects against chemical carcinogenesis and toxicity. The present report concerns the enhancement of dicoumarol-inhibited NAD(P)H:quinone reductase [NAD(P)H dehydrogenase (quinone); NAD(P)H:(quinone acceptor) oxidoreductase, EC 1.6.99.2] activity in mouse tissues in response to dietary administration of BHA. Cytosolic quinone reductase specific activity was increased significantly in 10 of 15 tissues examined from BHA-fed mice. The greatest proportionate increase, to 10 times control levels, was observed in liver. BHA also increased the quinone reductase activities of kidney, lung and the mucosa of the upper small intestine severalfold. The increases of quinone reductase activities in liver and digestive tissues in response to BHA were comparable to the increases previously observed in glutathione S-transferase (EC 2.5.1.18) and epoxide hydratase (EC 3.3.2.3) activities. Quinones are among the toxic products of oxidative metabolism of aromatic hydrocarbons. NAD(P)H:quinone reductase exhibits broad specificity for structurally diverse hydrophobic quinones, and may facilitate the microsomal metabolism of quinones to readily excreted conjugates. The protective effects of BHA appear to be due, at least in part, to the ability of this antioxidant to increase the activities in rodent tissues of several enzymes involved in the nonoxidative metabolism of a wide variety of xenobiotics.