Alda-1, an ALDH2 activator, protects against hepatic ischemia/reperfusion injury in rats via inhibition of oxidative stress
Alda-1, an ALDH2 activator, protects against hepatic ischemia/reperfusion injury in rats via inhibition of oxidative stress
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Alda-1 是一种 ALDH2 激活剂，通过抑制氧化应激来防止大鼠肝缺血/再灌注损伤
DOI：
10.1080/10715762.2018.1459042
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发表时间：
2018-04
影响因子：
3.3
通讯作者：
Huang Wen Qi
中科院分区：
文献类型：
--
作者：
Zhang Tao;Zhao Qiang;Ye Fang;Huang Chan yan;Chen Wan Mei;Huang Wen Qi
先前的研究证明，醛脱氢酶2 （ALDH2）的激活可以通过清除细胞毒性醛来减轻氧化应激，并对心脏、大脑和肺缺血/再灌注（I/R）损伤具有保护作用。在本研究中，我们研究了ALDH2激活剂Alda-1对肝I/R损伤的影响。Sprague-Dawley大鼠左、中肝叶局部热缺血1 h，再灌注6 h。大鼠缺血前30 min静脉注射Alda-1或载药。再灌注6 h后取大鼠血液和组织标本。检测组织损伤、促炎细胞因子、活性氧（ROS）、细胞凋亡、ALDH2表达和活性、4-羟基反式2-壬烯醛（4-HNE）和丙二醛（MDA）。BRL-3A肝细胞缺氧/再氧化（H/R）。测定细胞活力、活性氧和线粒体膜电位。Alda-1预处理可显著缓解I/ r诱导的丙氨酸转氨酶和天冬氨酸转氨酶升高，显著减弱肝脏病理损伤。此外，Alda-1显著抑制ROS和促炎细胞因子的产生、4-HNE和MDA的积累以及细胞凋亡。Alda-1给药后发现ALDH2活性升高。I/R后ALDH2表达无明显变化。H/R细胞的ROS也高于对照细胞，4-HNE处理后ROS升高，Alda-1处理后ROS降低。细胞活力和线粒体膜电位在H/R细胞中受到抑制，Alda-1处理后细胞活力和线粒体膜电位减弱。Alda-1激活ALDH2可通过清除细胞毒性醛来减轻肝I/R损伤。
Abstract Previous studies have proved that activation of aldehyde dehydrogenase two (ALDH2) can attenuate oxidative stress through clearance of cytotoxic aldehydes, and can protect against cardiac, cerebral, and lung ischemia/reperfusion (I/R) injuries. In this study, we investigated the effects of the ALDH2 activator Alda-1 on hepatic I/R injury. Partial warm ischemia was performed in the left and middle hepatic lobes of Sprague-Dawley rats for 1 h, followed by 6 h of reperfusion. Rats received either Alda-1 or vehicle by intravenous injection 30 min before ischemia. Blood and tissue samples of the rats were collected after 6-h reperfusion. Histological injury, proinflammatory cytokines, reactive oxygen species (ROS), cellular apoptosis, ALDH2 expression and activity, 4-hydroxy-trans-2-nonenal (4-HNE) and malondialdehyde (MDA) were measured. BRL-3A hepatocytes were subjected to hypoxia/reoxygenation (H/R). Cell viability, ROS, and mitochondrial membrane potential were determined. Pretreatment with Alda-1 significantly alleviated I/R-induced elevations of alanine aminotransferase and aspartate amino transferase, and significantly blunted the pathological injury of the liver. Moreover, Alda-1 significantly inhibited ROS and proinflammatory cytokines production, 4-HNE and MDA accumulation, and apoptosis. Increased ALDH2 activity was found after Alda-1 administration. No significant changes in ALDH2 expression were observed after I/R. ROS was also higher in H/R cells than in control cells, which was aggravated upon treatment with 4-HNE, and reduced by Alda-1 treatment. Cell viability and mitochondrial membrane potential were inhibited in H/R cells, which was attenuated upon Alda-1 treatment. Activation of ALDH2 by Alda-1 attenuates hepatic I/R injury via clearance of cytotoxic aldehydes.
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影响因子：
--
作者：
Ayala A;Muñoz MF;Argüelles S
通讯作者：
Argüelles S
影响因子：
3.8
作者：
Heijnen, BHM;Straatsburg, IH;van Gulik, TM
通讯作者：
van Gulik, TM
Alda-1 通过减少肺泡上皮细胞中的 4-Hydroxy-2-Nonenal 减轻肺缺血再灌注损伤
影响因子：
8.8
作者：
Ding, Jie;Zhang, Quanyi;Zhang, Hao
通讯作者：
Zhang, Hao
影响因子：
10.8
作者：
Gomes, Katia M. S.;Campos, Juliane C.;Ferreira, Julio C. B.
通讯作者：
Ferreira, Julio C. B.
影响因子：
2.4
作者：
Zhong, Zibiao;Hu, Qianchao;Ye, Qifa
通讯作者：
Ye, Qifa