Pretreatment with the ALDH2 agonist Alda-1 reduces intestinal injury induced by ischaemia and reperfusion in mice.
Many studies demonstrate that activation of aldehyde dehydrogenase 2 (ALDH2) protects against oxidative stress via detoxification of cytotoxic aldehydes, and could attenuate cardiac, cerebral, lung and renal ischaemia-reperfusion (I/R) injuries. However, the effect of ALDH2 in intestinal I/R is unknown. The present study was set up to determine whether an ALDH2 agonist, Alda-1, could alleviate intestinal injury after gut I/R. In a mouse model of intestinal I/R injury, histological grading, proinflammatory cytokines, oxidative stress, cellular apoptosis, chemokine contents, ALDH2 activity, 4-hydroxy-trans-2-nonenal (4-HNE) and malondialdehyde (MDA) were evaluated. The results indicated that I/R treatment conferred elevation in pathological scores, proinflammatory cytokines, oxidative stress, cellular apoptosis and chemokine levels, accompanied by accumulated 4-HNE and MDA. No significant changes in ALDH2 activity were observed after I/R. However, Alda-1 pretreatment significantly decreased these injurious indicators, concomitant with up-regulated ALDH2 activity, and lessened 4-HNE and MDA accumulation. Taken together, our results implicate activation of ALDH2 by Alda-1 in the significant abatement intestinal I/R injury.
Department of Parenteral and Enteral Nutrition, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, 100730, China.
Qiankun
Q
Zhu
Department of Parenteral and Enteral Nutrition, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, 100730, China hgzpumc@163.com.
Guizhen
G
He
Department of Parenteral and Enteral Nutrition, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, 100730, China.
Jie
J
Wang
Department of Parenteral and Enteral Nutrition, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, 100730, China.
Yukang
Y
Wang
Department of Parenteral and Enteral Nutrition, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, 100730, China.
Wei
W
Chen
D000071396:Aldehyde Dehydrogenase, Mitochondrial / Q000378:metabolism*; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides / Q000494:pharmacology / Q000627:therapeutic use*; D052117:Benzodioxoles / Q000494:pharmacology / Q000627:therapeutic use*; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004789:Enzyme Activation / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism; D007410:Intestinal Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008171:Lung Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D008297:Male; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051197:Toll-Like Receptor 4 / Q000378:metabolism
D000447:Aldehydes; D001549:Benzamides; D052117:Benzodioxoles; D018925:Chemokines; D016207:Cytokines; D018836:Inflammation Mediators; C531525:N-(1,3-benzodioxol-5-ylmethyl)-2,6-dichlorobenzamide; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C515029:ALDH2 protein, mouse; D000071396:Aldehyde Dehydrogenase, Mitochondrial
4-hydroxy-trans-2-nonenal; ALDH2; Alda-1; intestine; ischaemia–reperfusion injury; multiple organ dysfunction syndrome