Sulforaphane induces Nrf2 and protects against CYP2E1-dependent binge alcohol-induced liver steatosis.
Sulforaphane induces Nrf2 and protects against CYP2E1-dependent binge alcohol-induced liver steatosis.
复制标题
DOI：
10.1016/j.bbagen.2013.09.018
复制
发表时间：
2014-01
影响因子：
3
通讯作者：
Wu, Defeng
中科院分区：
文献类型：
--
作者：
Zhou, Richard;Lin, Jianjun;Wu, Defeng
酒精引起细胞损伤的机制尚不清楚，但主要机制似乎是脂质过氧化和氧化应激在酒精毒性中的作用。 CYP2E1 产生的 ROS 有助于乙醇诱导的氧化应激，抑制 CYP2E1 活性可减少乙醇诱导的脂肪肝。转录因子 Nrf2 调节许多细胞保护酶的表达，从而保护细胞免受多种毒素的侵害。目前的研究旨在评估萝卜硫素（一种 Nrf2 激活剂）在体内和体外减弱 CYP2E1 依赖性、乙醇诱导的脂肪变性的能力。萝卜硫素处理激活 Nrf2，增加 Nrf2 目标血红素加氧酶 -1 的水平，随后降低氧化应激，如急性乙醇处理后脂质过氧化和 3-硝基酪氨酸蛋白加合物的下降以及 GSH 水平的增加所示。它降低了乙醇升高的肝脏甘油三酯和胆固醇水平以及油红 O 染色。在体外，当向表达 CYP2E1 的 HepG2 E47 细胞中添加萝卜硫素时，也发现了类似的结果，提高了 Nrf2 水平，并减少了用乙醇培养的细胞中脂质的积累。萝卜硫素处理对 CYP2E1 的水平或活性没有影响。萝卜硫素被证明是小鼠急性乙醇诱导脂肪肝的有效体内抑制剂。 Nrf2 化学激活剂可能改善这些条件下发生的肝损伤，具有临床相关性，值得进一步研究。
The mechanism(s) by which alcohol causes cell injury are still not clear but a major mechanism appears to be the role of lipid peroxidation and oxidative stress in alcohol toxicity. CYP2E1-generated ROS contributes to the ethanol-induced oxidant stress and inhibition of CYP2E1 activity decreases ethanol-induced fatty liver. The transcription factor Nrf2 regulates the expression of many cytoprotective enzymes which results in cellular protection against a variety of toxins. The current study was designed to evaluate the ability of sulforaphane, an activator of Nrf2, to blunt CYP2E1-dependent, ethanol-induced steatosis in vivo and in vitro. The sulforaphane treatment activated Nrf2, increased levels of the Nrf2 target heme oxygenase -1 and subsequently lowered oxidant stress as shown by the decline in lipid peroxidation and 3-Nitrotyrosine protein adducts and an increase in GSH levels after the acute ethanol treatment. It decreased ethanol-elevated liver levels of triglycerides and cholesterol and Oil Red O staining. Similar results were found in vitro as addition of sulforaphane to HepG2 E47 cells, which express CYP2E1, elevated Nrf2 levels and decreased the accumulation of lipid in cells cultured with ethanol. Sulforaphane treatment had no effect on levels of or activity of CYP2E1. Sulforaphane proved to be an effective in vivo inhibitor of acute ethanol–induced fatty liver in mice. The possible amelioration of liver injury which occurs under these conditions by chemical activators of Nrf2 is of clinical relevance and worthy of further study.
登录
查看更多内容
影响因子：
6.7
作者：
通讯作者：
--
影响因子：
25.7
作者：
Butura, Angelica;Nilsson, Kerstin;Ingelman-Sundberg, Magnus
通讯作者：
Ingelman-Sundberg, Magnus
DOI：
10.1016/s0027-5107(97)00288-1
发表时间：
1998-06-18
影响因子：
2.3
作者：
Barceló, S;Macé, K;Chipman, JK
通讯作者：
Chipman, JK
影响因子：
6.1
作者：
DILUZIO, NR
通讯作者：
DILUZIO, NR
影响因子：
4.5
作者：
Gilmore, WJ;Hartmann, G;Kirby, GM
通讯作者：
Kirby, GM