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.
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Acknowledgments
This work was supported by the National Nature Science Foundation of China (no. 81373409 to Peng J), Hunan Provincial Natural Science Foundation of China (no. 13JJ2008 to Peng J), and Doctoral Fund of Ministry of Education of China (no. 20120162110056 to Peng J.)
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Fu SH and Zhang HF contributed equally to this work.
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Fu, SH., Zhang, HF., Yang, ZB. et al. Alda-1 reduces cerebral ischemia/reperfusion injury in rat through clearance of reactive aldehydes. Naunyn-Schmiedeberg's Arch Pharmacol 387, 87–94 (2014). https://doi.org/10.1007/s00210-013-0922-8
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DOI: https://doi.org/10.1007/s00210-013-0922-8