Butylated hydroxyanisole induces distinct expression patterns of Nrf2 and detoxification enzymes in the liver and small intestine of C57BL/6 mice
Butylated hydroxyanisole induces distinct expression patterns of Nrf2 and detoxification enzymes in the liver and small intestine of C57BL/6 mice
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丁基羟基苯甲醚诱导 C57BL/6 小鼠肝脏和小肠中 Nrf2 和解毒酶的独特表达模式
DOI：
10.1016/j.taap.2015.08.006
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发表时间：
2015-11-01
影响因子：
3.8
通讯作者：
Wang, Xiu Jun
中科院分区：
文献类型：
--
作者：
Luo, Lin;Chen, Yeru;Wang, Xiu Jun
丁基羟基茴香醚（BHA）作为抗氧化剂和防腐剂广泛应用于食品、食品包装和医药等领域。其化学预防特性归因于其激活转录因子NF-E2 p45相关因子2（Nrf2）的能力，Nrf2指导解毒和保护免受氧化应激的中心遗传程序。本研究旨在观察BHA诱导的野生型（WT）和Nrf2（-/-）小鼠中Nrf2及其调节的II相酶Nqo 1、AKR1B8和Ho-1的组织学变化。小鼠每天口服200 mg/kg BHA，持续3天。免疫组织化学显示，在WT小鼠的肝脏中，BHA增加了肝细胞中的Nqo 1染色，主要在中央周围区域。相反，AKR1B8的诱导主要出现在门静脉周围区域的肝细胞中。基础型和诱导型Ho-1几乎全部位于枯否细胞。在野生型小鼠小肠中，Nqo 1和AKR1B8的诱导表达模式与Nrf 2的诱导表达模式几乎相同，在绒毛中的表达比在隐窝中的表达更强。相反，Keap1在增殖细胞所在的隐窝中表达更高。我们的研究表明，BHA在WT小鼠的肝脏和小肠中引起II期解毒酶的差异表达模式，但在Nrf2（-/-）小鼠中没有，表明了对BHA的体内细胞类型特异性反应。(C)2015 Elsevier Inc. All rights reserved.
Butylated hydroxyanisole (BHA) is widely used as an antioxidant and preservative in food, food packaging and medicines. Its chemopreventive properties are attributing to its ability to activate the transcription factor NF-E2 p45-related factor 2 (Nrf2), which directs central genetic programs of detoxification and protection against oxidative stress. This study was to investigate the histological changes of Nrf2 and its regulated phase II enzymes Nqo1,AKR1B8, and Ho-1 in wild-type (WT) and Nrf2(-/-) mice induced by BHA. The mice were given a 200 mg/kg oral dose of BHA daily for three days. Immunohistochemistry revealed that, in the liver from WT mice, BHA increased Nqo1 staining in hepatocytes, predominately in the pericentral region. In contrast, the induction of AKR1B8 appeared mostly in hepatocytes in the periportal region. The basal and inducible Ho-1 was located almost exclusively in Kupffer cells. In the small intestine from WT mice, the inducible expression patterns of Nqo1 and AKR1B8 were nearly identical to that of Nrf2, with more intense staining in the villus than that the crypt. Conversely, Keap1 was more highly expressed in the crypt, where the proliferative cells reside. Our study demonstrates that BHA elicited differential expression patterns of phase II-detoxifying enzymes in the liver and small intestine from WT but not Nrf2(-/-) mice, demonstrating a cell type specific response to BHA in vivo. (C) 2015 Elsevier Inc. All rights reserved.