Protective effect of quercetin on lead-induced oxidative stress and endoplasmic reticulum stress in rat liver via the IRE1/JNK and PI3K/Akt pathway
Protective effect of quercetin on lead-induced oxidative stress and endoplasmic reticulum stress in rat liver via the IRE1/JNK and PI3K/Akt pathway
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DOI：
10.3109/10715762.2012.760198
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发表时间：
2013-03-01
影响因子：
3.3
通讯作者：
Cheng, C.
中科院分区：
文献类型：
--
作者：
Liu, C. -M.;Zheng, G. H.;Cheng, C.
铅是一种著名的环境毒素，是危害人类健康的主要毒物之一。槲皮素(QE)是一种天然黄酮类化合物，具有多种药用价值和药用价值。然而，其对铅诱导的肝脏内质网(ER)应激的保护作用尚不清楚。本研究旨在探讨槲皮素对染铅大鼠肝脏内质网应激的影响。将Wistar大鼠暴露于饮用醋酸铅的水中，同时给予或不联合给予槲皮素，共染毒75天。我们的数据显示，无论是肝损伤的诊断指标还是组织病理学分析都表明，槲皮素以剂量依赖的方式显著地阻止了铅所致的肝毒性。槲皮素能显著降低血液和肝脏中铅含量。Western印迹分析表明，槲皮素能显著抑制铅诱导的大鼠肝脏内质网应激。在探索其潜在作用机制的过程中，我们发现其对铅诱导的氧化应激有明显的抑制作用。槲皮素可降低大鼠肝脏中ROS的生成，提高总抗氧化能力。此外，Quercetin显著增加大鼠肝脏中磷脂酰肌醇-3-激酶(PI3K)和磷酸化蛋白激酶B(PKB/Akt)的水平。在所研究的未折叠蛋白反应(UPR)通路中，槲皮素显著抑制铅诱导的大鼠肝脏磷酸化肌醇需求酶1(IRE1)和c-Jun氨基末端激酶(JNK)的增加。综上所述，这些结果表明，槲皮素抑制铅诱导的内质网应激至少部分是由于其抗氧化应激活性及其调节PI3K/Akt和IRE1/JNK信号通路的能力。
Lead (Pb), a well-known environmental toxin, is one of the major hazards for human health. Quercetin (QE), a natural flavonoid, has been reported to have many benefits and medicinal properties. However, its protective effects against Pb-induced endoplasmic reticulum (ER) stress in liver have not been clarified. The aim of the present study was to investigate the effects of quercetin on hepatic ER stress in rats exposed to Pb. Wistar rats were exposed to lead acetate in the drinking water with or without quercetin co-administration for 75 days. Our data showed that quercetin significantly prevented Pb-induced hepatotoxicity in a dose-dependent manner, indicated by both diagnostic indicators of liver damage and histopathological analysis. Quercetin markedly decreased Pb contents in blood and liver. Western blot analysis showed that Pb-induced ER stress in rat liver was significantly inhibited by quercetin. In exploring the underlying mechanisms of quercetin action, we found quercetin markedly suppressed Pb-induced oxidative stress. Quercetin decreased reactive oxygen species (ROS) production and increased the total antioxidant capacity in rat livers. Additionally, quercetin dramatically increased Phosphoinositide-3-kinase (PI3K) and phosphorylated protein kinase B (PKB/Akt) levels in liver rats. In the examined unfolded protein response (UPR) pathways, quercetin markedly inhibited the Pb-induced increase of the phosphorylated inositol-requiring enzyme 1 (IRE1) and c-jun N-terminal kinase (JNK) in rat liver. Taken together, these results suggested that the inhibition of Pb-induced ER stress by quercetin is due at least in part to its anti-oxidant stress activity and its ability to modulate the PI3K/Akt and IRE1/JNK signaling pathway.