Acrolein induces axolemmal disruption, oxidative stress, and mitochondrial impairment in spinal cord tissue.
Acrolein, a byproduct of oxidative stress and lipid peroxidation, has been implicated in neurodegenerative disorders such as Alzheimer's disease, but not in spinal cord trauma, as a possible key factor in neuronal degeneration. Using an isolated guinea pig spinal cord model, we have found that acrolein, in a dose- and time-dependent manner, inflicts severe membrane disruption, a factor thought to be critical in triggering axonal deterioration and cell death. The concentration threshold of such detrimental effect is shown to be around 1 microM when acrolein was exposed for 4 h. The membrane damage is likely mediated in part by reactive oxygen species and lipid peroxidation, which were elevated in response to acrolein exposure. Antioxidants were able to significantly reduce acrolein-mediated membrane disruption which further supports the role of reactive oxygen species in the loss of membrane integrity. Mitochondrial function was also impaired after acrolein exposure which not only implicates but emphasizes the role of this organelle in reactive oxygen species generation. In summary, our data strongly suggest that at a clinically relevant concentration, acrolein can severely compromise membrane integrity and may further serve as an initiating toxin triggering secondary injury cascades following the initial physical insult to the spinal cord.
Luo
Jian
J
Department of Basic Medical Sciences, Center for Paralysis Research, Institute for Applied Neurology, School of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA.
Shi
Riyi
R
D000171:Acrolein / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001369:Axons / Q000473:pathology*; D002462:Cell Membrane / Q000187:drug effects / Q000473:pathology; D004996:Ethidium; D005260:Female; D005456:Fluorescent Dyes; D006168:Guinea Pigs; D006735:Horseradish Peroxidase; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008928:Mitochondria / Q000473:pathology*; D018384:Oxidative Stress / Q000187:drug effects*; D013116:Spinal Cord / Q000473:pathology*; D013119:Spinal Cord Injuries / Q000473:pathology*; D013574:Synaptosomes / Q000187:drug effects / Q000473:pathology; D013778:Tetrazolium Salts; D013844:Thiazoles
D000975:Antioxidants; D005456:Fluorescent Dyes; D013778:Tetrazolium Salts; D013844:Thiazoles; D000171:Acrolein; D007770:L-Lactate Dehydrogenase; D006735:Horseradish Peroxidase; D004996:Ethidium; C022616:thiazolyl blue