title: Dimercaprol is an acrolein scavenger that mitigates acrolein-mediated PC-12 cells toxicity and reduces acrolein in rat following spinal cord injury.
abstract: Acrolein is one of the most toxic byproducts of lipid peroxidation, and it has been shown to be associated with multiple pathological processes in trauma and diseases, including spinal cord injury, multiple sclerosis, and Alzheimer's disease. Therefore, suppressing acrolein using acrolein scavengers has been suggested as a novel strategy of neuroprotection. In an effort to identify effective acrolein scavengers, we have confirmed that dimercaprol, which possesses thiol functional groups, could bind and trap acrolein. We demonstrated the reaction between acrolein and dimercaprol in an abiotic condition by nuclear magnetic resonance spectroscopy. Specifically, dimercaprol is able to bind to both the carbon double bond and aldehyde group of acrolein. Its acrolein scavenging capability was further demonstrated by in vitro results that showed that dimercaprol could significantly protect PC-12 cells from acrolein-mediated cell death in a dose-dependent manner. Furthermore, dimercaprol, when applied systemically through intraperitoneal injection, could significantly reduce acrolein contents in spinal cord tissue following a spinal cord contusion injury in rats, a condition known to have elevated acrolein concentration. Taken together, dimercaprol may be an effective acrolein scavenger and a viable candidate for acrolein detoxification.
authors.affiliation: Department of Basic Medical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana, USA.|Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, USA.
authors.forename: Ran
authors.initials: R
authors.lastname: Tian
authors.affiliation: Department of Basic Medical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana, USA.|Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, USA.
authors.forename: Riyi
authors.identifier: 0000-0002-7297-9428
authors.initials: R
authors.lastname: Shi
mesh_terms: D000171:Acrolein / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D004112:Dimercaprol / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D016716:PC12 Cells / Q000187:drug effects; D051381:Rats; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology
chemical_list: D016166:Free Radical Scavengers; D004112:Dimercaprol; D000171:Acrolein; D007770:L-Lactate Dehydrogenase
keywords: acrolein; dimercaprol (BAL); oxidative stress