Acrolein scavenging: a potential novel mechanism of attenuating oxidative stress following spinal cord injury.
It has long been established that oxidative stress plays a critical role in the pathophysiology of spinal cord injury, and represents an important target of therapeutic intervention following the initial trauma. However, free radical scavengers have been largely ineffective in clinical trials, and as such a novel target to attenuate oxidative stress is highly warranted. In addition to free radicals, peroxidation of lipid membranes following spinal cord injury (SCI) produces reactive aldehydes such as acrolein. Acrolein is capable of depleting endogenous antioxidants such as glutathione, generating free radicals, promoting oxidative stress, and damaging proteins and DNA. Acrolein has a significantly longer half-life than the transient free radicals, and thus may represent a potentially better target of therapeutic intervention to attenuate oxidative stress. There is growing evidence, from our lab and others, to suggest that reactive aldehydes such as acrolein play a critical role in oxidative stress and SCI. The focus of this review is to summarize the cellular and biochemical mechanisms of acrolein-induced membrane damage, mitochondrial injury, oxidative stress, cell death, and functional loss. Evidence will also be presented to suggest that acrolein scavenging may be a novel means of therapeutic intervention to attenuate oxidative stress and improve recovery following traumatic SCI.
Department of Basic Medical Sciences, School of Veterinary Medicine, Center for Paralysis Research, Purdue University, West Lafayette, Indiana 47907, USA.
Kristin
K
Hamann
Riyi
R
Shi
D000171:Acrolein / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D016166:Free Radical Scavengers / Q000378:metabolism; D006801:Humans; D006830:Hydralazine / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008954:Models, Biological; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*
D016166:Free Radical Scavengers; D006830:Hydralazine; D000171:Acrolein