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Hydralazine inhibits compression and acrolein‐mediated injuries in ex vivo spinal cord
Author(s) -
Hamann Kristin,
Nehrt Genevieve,
Ouyang Hui,
Duerstock Brad,
Shi Riyi
Publication year - 2008
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.05002.x
Subject(s) - acrolein , hydralazine , lipid peroxidation , oxidative stress , ex vivo , pharmacology , spinal cord injury , chemistry , spinal cord , neuroprotection , glutathione , medicine , anesthesia , endocrinology , biochemistry , in vitro , psychiatry , blood pressure , enzyme , catalysis
We have previously shown that acrolein, a lipid peroxidation byproduct, is significantly increased following spinal cord injury in vivo , and that exposure to neuronal cells results in oxidative stress, mitochondrial dysfunction, increased membrane permeability, impaired axonal conductivity, and eventually cell death. Acrolein thus may be a key player in the pathogenesis of spinal cord injury, where lipid peroxidation is known to be involved. The current study demonstrates that the acrolein scavenger hydralazine protects against not only acrolein‐mediated injury, but also compression in guinea pig spinal cord ex vivo . Specifically, hydralazine (500 μmol/L to 1 mmol/L) can significantly alleviate acrolein (100–500 μmol/L)‐induced superoxide production, glutathione depletion, mitochondrial dysfunction, loss of membrane integrity, and reduced compound action potential conduction. Additionally, 500 μmol/L hydralazine significantly attenuated compression‐mediated membrane disruptions at 2 and 3 h following injury. This was consistent with our findings that acrolein‐lys adducts were increased following compression injury ex vivo , an effect that was prevented by hydralazine treatment. These findings provide further evidence for the role of acrolein in spinal cord injury, and suggest that acrolein‐scavenging drugs such as hydralazine may represent a novel therapy to effectively reduce oxidative stress in disorders such as spinal cord injury and neurodegenerative diseases, where oxidative stress is known to play a role.