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 mumol/L to 1 mmol/L) can significantly alleviate
acrolein (100-500 mumol/L)-induced
superoxide production,
glutathione depletion,
mitochondrial dysfunction, loss of membrane integrity, and reduced compound action potential conduction. Additionally, 500 mumol/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.