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.