RGD Reference Report - Alda-1, an ALDH2 activator, protects against hepatic ischemia/reperfusion injury in rats via inhibition of oxidative stress. - Rat Genome Database

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

Authors: Zhang, Tao  Zhao, Qiang  Ye, Fang  Huang, Chan-Yan  Chen, Wan-Mei  Huang, Wen-Qi 
Citation: Zhang T, etal., Free Radic Res. 2018 Jun;52(6):629-638. doi: 10.1080/10715762.2018.1459042. Epub 2018 Apr 13.
RGD ID: 14975297
Pubmed: (View Article at PubMed) PMID:29589772
DOI: Full-text: DOI:10.1080/10715762.2018.1459042

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.


Disease Annotations    

Gene-Chemical Interaction Annotations    
Objects Annotated

Genes (Rattus norvegicus)
Aldh2  (aldehyde dehydrogenase 2 family member)

Genes (Mus musculus)
Aldh2  (aldehyde dehydrogenase 2, mitochondrial)

Genes (Homo sapiens)
ALDH2  (aldehyde dehydrogenase 2 family member)

Additional Information