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二巯丙醇是一种丙烯醛清除剂,可减轻丙烯醛介导的PC-12细胞毒性,并降低大鼠脊髓损伤后的丙烯醛水平。

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

作者信息

Tian Ran, Shi Riyi

机构信息

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.

出版信息

J Neurochem. 2017 Jun;141(5):708-720. doi: 10.1111/jnc.14025. Epub 2017 May 3.

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.

摘要

丙烯醛是脂质过氧化作用中最具毒性的副产物之一,并且已表明它与创伤和疾病中的多种病理过程相关,包括脊髓损伤、多发性硬化症和阿尔茨海默病。因此,使用丙烯醛清除剂抑制丙烯醛已被提议作为一种神经保护的新策略。为了确定有效的丙烯醛清除剂,我们已证实具有硫醇官能团的二巯丙醇能够结合并捕获丙烯醛。我们通过核磁共振光谱法在非生物条件下证明了丙烯醛与二巯丙醇之间的反应。具体而言,二巯丙醇能够与丙烯醛的碳双键和醛基结合。体外实验结果进一步证明了其丙烯醛清除能力,结果表明二巯丙醇能够以剂量依赖的方式显著保护PC - 12细胞免受丙烯醛介导的细胞死亡。此外,当通过腹腔注射全身应用二巯丙醇时,它能够显著降低大鼠脊髓挫伤损伤后脊髓组织中的丙烯醛含量,在这种情况下已知丙烯醛浓度会升高。综上所述,二巯丙醇可能是一种有效的丙烯醛清除剂,也是丙烯醛解毒的可行候选物。

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