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.

Neuroprotective effect of safranal, an active ingredient of Crocus sativus , in a rat model of transient cerebral ischemia

“…Several phenomena observed during brain ischemia and reperfusion can be attributed to damage to membrane lipids, especially by lipolysis during ischemia and by radical-mediated peroxidation of polyunsaturated fatty acids [31]. Lipid peroxidation is one of the major mechanisms responsible for the cellular damage caused by oxidative stress, and MDA is one of the main end products of lipid peroxidation which is accumulated during ischemia/reperfusion [5]. Hoseinzadeh et al found that safranal significantly reduced the MDA level in the rat hippocampus [10].…”

Mitochondrial Aldehyde Dehydrogenase Activation by Alda‐1 Inhibits Atherosclerosis and Attenuates Hepatic Steatosis in Apolipoprotein E‐Knockout Mice

“…Recently, the beneficial influence of ALDH2 stimulation in acute ischemia‐reperfusion injury of heart or brain has been attributed to many possible mechanisms, including attenuation of oxidative stress and clearance of reactive aldehydes, 26 improvement of mitochondrial function and decrease of apoptosis, 27 and augmentation 28 or inhibition of autophagy. 29 In our setting, Alda‐1 tended to decrease the content of 4‐HNE protein adducts and nitrotyrosine in atherosclerotic plaques, but such action did not reached statistical significance.…”

Up-regulation of brain-enriched miR-107 promotes excitatory neurotoxicity through down-regulation of glutamate transporter-1 expression following ischaemic stroke

“…The method for sample preparation was described previously by Fu et al [5]. For Western blot analysis, samples containing 20-60 μg of total protein were subjected to SDS/PAGE (10 % gel) and the proteins were transferred on to PVDF membranes.…”