4.5 Article

Dimercaprol is an acrolein scavenger that mitigates acrolein-mediated PC-12 cells toxicity and reduces acrolein in rat following spinal cord injury

Journal

JOURNAL OF NEUROCHEMISTRY
Volume 141, Issue 5, Pages 708-720

Publisher

WILEY
DOI: 10.1111/jnc.14025

Keywords

acrolein; dimercaprol (BAL); oxidative stress

Funding

  1. Indiana State Department of Health [204200]
  2. National Institutes of Health [NS073636]
  3. Indiana CTSI Collaboration in Biomedical Translational Research (CBR/CTR) Pilot Program Grant [RR025761]

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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.

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