Alda-1, an ALDH2 activator, protects against hepatic ischemia/reperfusion injury in rats via inhibition of oxidative stress

作者：Tao Zhang, Qiang Zhao, Fang Ye, Chanyan Huang, Wanmei Chen, Wenqi Huang · 发表于：Free Radical Research · 年份：2018 · DOI：10.1080/10715762.2018.1459042 · 被引用次数：57 · 研究领域：Liver Disease and Transplantation、Liver Disease Diagnosis and Treatment、Alcohol Consumption and Health Effects

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 cell...