Emodin induces liver injury by inhibiting the key enzymes of FADH/NADPH transport in rat liver
Emodin induces liver injury by inhibiting the key enzymes of FADH/NADPH transport in rat liver
复制标题
大黄素通过抑制大鼠肝脏FADH/NADPH转运关键酶诱导肝损伤
DOI：
10.1039/c7tx00307b
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发表时间：
2018
影响因子：
2.1
通讯作者：
Hongbin Xiao
中科院分区：
文献类型：
--
作者：
Xiaowei Yang;Yinhuan Zhang;Yan Liu;Chang Chen;Wenjuan Xu;Hongbin Xiao
大黄素是一种天然蒽醌衍生物，存在于许多中草药中。可能引起肝损害，但其机制尚不清楚。本研究采用7组SD大鼠，分别给予3个剂量的大黄素。通过生化指标分析和组织病理学观察肝损伤情况。应用蛋白质组学技术检测对照组（CG）和肝损伤组之间蛋白质的变化。结果表明，大黄素引起肝损伤具有时间和剂量依赖性。大黄素1周高剂量组（HG 1）甘油醛-3-磷酸脱氢酶（GAPDH）表达下调，苹果酸脱氢酶（MDH）活性被大黄素抑制。这可能导致FADH或NADH/NADPH从细胞质向线粒体转运的抑制。WB结果显示，FADH/NADPH转运抑制诱导了caspase-9和caspase-3的高活性，细胞色素C（Cyt C）、caspase-9和caspase-3的高表达，可能导致线粒体凋亡途径的激活。此外，无论是高剂量组还是低剂量组，大黄素对线粒体的影响均不明显。总的来说，我们首次发现大黄素抑制质子转运并诱导线粒体凋亡途径的激活，这可能是肝损伤的原因。
Emodin is a natural anthraquinone derivative that occurs in many Chinese medicinal herbs. It might induce liver damage, but the mechanism is not clear. In this research, seven groups of Sprague-Dawley (SD) rats with three doses of emodin were used. The liver injury was examined by analyzing biochemical indexes and histopathology. Altered proteins between the control group (CG) and the liver injury group were determined by proteomic technology. The results showed that emodin causes liver injury in a time- and dose-dependent manner. In the high-dosage 1-week group (HG1), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was downregulated, and the activity of malate dehydrogenase (MDH) was inhibited by emodin. These might cause the inhibition of FADH or NADH/NADPH transport from the cytoplasm to mitochondria. The WB results showed that the inhibition of FADH/NADPH transport induced a high activity of caspase-9 and caspase-3, and the expressions of cytochrome c (Cyt C), caspase-9 and caspase-3 were high in HG1, which might lead to mitochondrial apoptosis pathway activation. In addition, whatever the HG1 or low-dose group (LG), the effects of emodin on mitochondria were observed. Overall, for the first time, we showed that emodin inhibited proton transport and induced the activation of the mitochondrial apoptosis pathway, which might be the reason for liver injury.