Vitamin E inhibits hepatic NF-κB activation in rats administered the hepatic tumor promoter, phenobarbital
Vitamin E inhibits hepatic NF-κB activation in rats administered the hepatic tumor promoter, phenobarbital
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DOI：
10.1093/jn/131.10.3178
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发表时间：
2002-10-01
影响因子：
4.2
通讯作者：
Glauert, HP
中科院分区：
文献类型：
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作者：
Calfee-Mason, KG;Spear, BT;Glauert, HP
苯巴比妥（PB）是一种有效的肝肿瘤促进剂。虽然PB的促进活性可能与改变的细胞增殖或凋亡有关，但氧化应激环境的诱导也可能是重要的。PB已显示激活转录因子核因子-κ B（NF-κ B）。在这项研究中，我们假设PB诱导的NF-κ B活化可以通过饮食维生素E降低大鼠。雄性Sprague-Dawley大鼠（n = 39）被喂食具有不同水平的膳食维生素E（10、50或250 mg/kg的d/-α-生育酚乙酸酯）的纯化饮食28 d，此时每种膳食维生素E水平的8只大鼠被喂食具有500 mg/kg PB的相同饮食10 d。在喂食低维生素E饮食的大鼠中，PB增加了NF-κ B DNA结合，但它不影响喂食高水平维生素E（50和250 mg/kg）的大鼠中NF-κ B的活化。维生素E也可以通过增强其他抗氧化剂来降低PB产生的氧化应激;因此，我们还测量了肝脏谷胱甘肽S-转移酶、谷胱甘肽过氧化物酶、谷胱甘肽还原酶、超氧化物歧化酶、过氧化氢酶和NAD（P）H：醌还原酶（DT-心肌黄酶）活性以及谷胱甘肽和抗坏血酸浓度。增加膳食α-生育酚并没有影响PB治疗改变的抗氧化剂和抗氧化酶。因此，α-生育酚乙酸酯对NF-κ B活化的影响似乎不是由抗氧化系统的改变介导的。这些结果表明，NF-κ B（一种影响细胞增殖和凋亡相关基因表达的转录因子）的激活可被膳食维生素E抑制。
Phenobarbital (PB) is an efficacious hepatic tumor promoter. Although the promoting activity of PB is likely related to altered cell proliferation or apoptosis, the induction of an oxidative stress environment may also be important. PB has been shown to activate the transcription factor nuclear factor-kappaB (NF-kappaB). In this study, we hypothesized that PB-induced NF-kappaB activation can be decreased by dietary vitamin E in rats. Male Sprague-Dawley rats (n = 39) were fed a purified diet with varying levels of dietary vitamin E (10, 50 or 250 mg/kg of d/-alpha-tocopherol acetate) for 28 d, at which time 8 rats per level of dietary vitamin E were fed the same diet with 500 mg/kg PB for 10 d. In the rats fed the low vitamin E diet, PB increased NF-kappaB DNA binding, but it did not affect NF-kappaB activation in rats fed higher levels of vitamin E (50 and 250 mg/kg). Vitamin E may decrease the oxidative stress created by PB by also enhancing other antioxidants; therefore, we also measured hepatic glutathione S-transferase, glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase and NAD(P)H: quinone reductase (DT-diaphorase) activities and glutathione and ascorbic acid concentrations. Increased dietary alpha-tocopherol did not affect the antioxidants and antioxidant enzymes altered by PB treatment. Thus, the effect of alpha-tocopherol acetate on NF-kappaB activation does not appear to be mediated by alterations in the antioxidant system. These results demonstrate that the activation of NF-kappaB, a transcription factor that affects cell proliferation- and apoptosis-related gene expression, can be inhibited by dietary vitamin E.