Pomegranate prevents binge alcohol-induced gut leakiness and hepatic inflammation by suppressing oxidative and nitrative stress.
Pomegranate prevents binge alcohol-induced gut leakiness and hepatic inflammation by suppressing oxidative and nitrative stress.
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DOI：
10.1016/j.redox.2018.07.012
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发表时间：
2018-09
期刊：
影响因子：
11.4
通讯作者：
Song BJ
中科院分区：
文献类型：
--
作者：
Cho YE;Song BJ
酒精性肝病（ALD）是世界范围内的一种主要慢性肝病，其范围可以从简单的脂肪变性、炎症到纤维化/肝硬化，可能通过肠漏和全身性内毒素血症。我们研究了石榴（POM）是否可以防止酗酒引起的肠道渗漏，内毒素血症和炎症性肝损伤。POM预处理10天后，大鼠暴露于3个口服剂量的酗酒（5 g/kg/剂量）或葡萄糖（作为对照），间隔12小时。酗酒暴露通过增加小肠和肝脏中氧化和硝化应激标记蛋白（如乙醇诱导型CYP 2 E1、诱导型一氧化氮合酶和硝化蛋白）的水平，诱导肠漏伴血浆内毒素显著升高和炎症性脂肪肝。POM预处理通过抑制氧化和硝化应激标志蛋白的升高，显著降低了酒精诱导的肠屏障功能障碍、血浆内毒素和炎症性肝病。POM预处理显著恢复了肠紧密连接（TJ）蛋白的水平，如ZO-1，occludin，claudin-1和claudin-3在酒精暴露后显著减少。此外，肠粘附连接（AJ）蛋白（例如，β-连环蛋白和E-钙粘蛋白）和桥粒斑珠蛋白沿着相关蛋白α-微管蛋白在酗酒暴露的大鼠中明显降低，但在POM预处理的大鼠中恢复到基础水平。免疫沉淀，免疫印迹分析显示，肠claudin-1蛋白被硝化和泛素化的酒精暴露大鼠，而这些修改被显着阻止POM预处理。这些结果首次表明，POM可以通过抑制氧化和硝化应激来防止酒精诱导的肠漏和炎症性肝损伤。
Alcoholic liver disease (ALD) is a major chronic liver disease worldwide and can range from simple steatosis, inflammation to fibrosis/cirrhosis possibly through leaky gut and systemic endotoxemia. We investigated whether pomegranate (POM) protects against binge alcohol-induced gut leakiness, endotoxemia, and inflammatory liver damage. After POM pretreatment for 10 days, rats were exposed to 3 oral doses of binge alcohol (5 g/kg/dose) or dextrose (as control) at 12-h intervals. Binge alcohol exposure induced leaky gut with significantly elevated plasma endotoxin and inflammatory fatty liver by increasing the levels of oxidative and nitrative stress marker proteins such as ethanol-inducible CYP2E1, inducible nitric oxide synthase, and nitrated proteins in the small intestine and liver. POM pretreatment significantly reduced the alcohol-induced gut barrier dysfunction, plasma endotoxin and inflammatory liver disease by inhibiting the elevated oxidative and nitrative stress marker proteins. POM pretreatment significantly restored the levels of intestinal tight junction (TJ) proteins such as ZO-1, occludin, claudin-1, and claundin-3 markedly diminished after alcohol-exposure. In addition, the levels of gut adherent junction (AJ) proteins (e.g., β-catenin and E-cadherin) and desmosome plakoglobin along with associated protein α-tubulin were clearly decreased in binge alcohol-exposed rats but restored to basal levels in POM-pretreated rats. Immunoprecipitation followed by immunoblot analyses revealed that intestinal claudin-1 protein was nitrated and ubiquitinated in alcohol-exposed rats, whereas these modifications were significantly blocked by POM pretreatment. These results showed for the first time that POM can prevent alcohol-induced gut leakiness and inflammatory liver injury by suppressing oxidative and nitrative stress.
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影响因子：
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作者：
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DOI：
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影响因子：
7.4
作者：
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影响因子：
7.4
作者：
Abdelmegeed, Mohamed A.;Banerjee, Atrayee;Jang, Sehwan;Yoo, Seong-Ho;Yun, Jun-Won;Gonzalez, Frank J.;Keshavarzian, Ali;Song, Byoung-Joon
通讯作者：
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