Determination of urine 3-HPMA, a stable acrolein metabolite in a rat model of spinal cord injury

Lingxing Zheng, Jonghyuck Park, Michael Walls, Melissa Tully, Amber Jannasch, Bruce Cooper, Riyi Shi

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Acrolein has been suggested to be involved in a variety of pathological conditions. The monitoring of acrolein is of significant importance in delineating the pathogenesis of various diseases. Aimed at overcoming the reactivity and volatility of acrolein, we describe a specific and stable metabolite of acrolein in urine, N-acetyl-S-3-hydroxypropylcysteine (3-HPMA), as a potential surrogate marker for acrolein quantification. Using the LC/MS/MS method, we demonstrated that 3-HPMA was significantly elevated in a dose-dependent manner when acrolein was injected into rats IP or directly into the spinal cord, but not when acrolein scavengers were co-incubated with acrolein solution. A nonlinear mathematic relationship is established between acrolein injected directly into the spinal cord and a correlated dose-dependent increase of 3-HPMA, suggesting the increase of 3-HPMA becomes less apparent as the level of injected acrolein increases. The elevation of 3-HPMA was further detected in the rat spinal cord injury, a pathological condition known to be associated with elevated endogenous acrolein. This finding was further validated by concomitant confirmation of increased acrolein-lysine adducts using established dot immunoblotting techniques. The noninvasive nature of measuring 3-HPMA concentrations in urine allows for long-term monitoring of acrolein in the same animal and ultimately in human clinical studies. Due to wide spread involvement of acrolein in human health, the benefits of this study have the potential to enhance human health significantly.

Original languageEnglish
Pages (from-to)1334-1341
Number of pages8
JournalJournal of Neurotrauma
Volume30
Issue number15
DOIs
StatePublished - Aug 1 2013

Keywords

  • Lipid peroxidation
  • Liquid chromatography
  • Mass spectrometry
  • Oxidative stress

ASJC Scopus subject areas

  • Clinical Neurology

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