Alda-1 reduces cerebral ischemia/reperfusion injury in rat through clearance of reactive aldehydes.

Abstract

Many studies demonstrate that accumulation of reactive aldehydes plays an important role in cellular oxidative injury and aldehyde dehydrogenase 2 (ALDH2)-mediated detoxification of reactive aldehydes is thought as an endogenous protective mechanism against cell injury. This study was performed to explore whether Alda-1, a newly identified ALDH2 activator, was able to protect brain against ischemia/reperfusion injury through clearance of reactive aldehydes. In a rat model of focal cerebral ischemia/reperfusion injury, neurological function, infarct volume, cellular apoptosis, mortality, ALDH2 activity and protein expression, contents of 4-hydroxy-2-nonenal (4-HNE), and malondialdehyde (MDA) were determined. The results showed that ischemia/reperfusion treatment led to increase in neurological deficit score, infarct volume, cellular apoptosis, and mortality accompanied by the elevated levels of reactive aldehydes (4-HNE and MDA). There was no significant change in ALDH2 activity and protein expression. Alda-1 treatment at both dosages (15 mg/kg × 2 or 50 mg/kg × 2, i.g.) was able to increase the activity of ALDH2 and decrease the accumulation of reactive aldehydes concomitantly with the improvement of brain injury (decrease in infarct volume, cellular apoptosis, and mortality) and neurological function (decrease in neurological deficit score). However, Alda-1 treatment did not affect ALDH2 protein expression. Our results suggest that the protective effect of Alda-1 on cerebral ischemia/reperfusion injury is related to ALDH2 activation and clearance of reactive aldehydes.

• Authors: Si-Hai Fu, Hong-Feng Zhang, Zhong-Bao Yang, Ting-Bo Li, Bin Liu, Zheng Lou, Qi-Lin Ma, Xiu-Ju Luo, Jun Peng
• Journal: Naunyn-Schmiedeberg's archives of pharmacology (Naunyn Schmiedebergs Arch Pharmacol) Vol. 387 Issue 1 Pg. 87-94 (Jan 2014) ISSN: 1432-1912 [Electronic] Germany
• PMID: 24081521 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aldehydes
• Benzamides
• Benzodioxoles
• Mitochondrial Proteins
• N-(1,3-benzodioxol-5-ylmethyl)-2,6-dichlorobenzamide
• Neuroprotective Agents
• Aldehyde Dehydrogenase
• Aldehyde Dehydrogenase, Mitochondrial
• Aldh2 protein, rat

Topics

• Aldehyde Dehydrogenase (metabolism)
• Aldehyde Dehydrogenase, Mitochondrial
• Aldehydes (metabolism)
• Animals
• Benzamides (pharmacology, therapeutic use)
• Benzodioxoles (pharmacology, therapeutic use)
• Brain Ischemia (drug therapy, metabolism)
• Male
• Metabolic Clearance Rate (drug effects, physiology)
• Mitochondrial Proteins (metabolism)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Random Allocation
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (drug therapy, metabolism)