Two drugs have been shown to be effective in reducing acrolein levels in the body: hydralazine and phenelzine, which have been approved by the U.S. Food and Drug Administration for hypertension and depression, respectively.The testing method could be used in conjunction with other measures to test patients for the progress of spinal cord disease.
1 Department of Basic Medical Sciences, School of Veterinary Medicine
2 Weldon School of Biomedical Engineering, Purdue University
3 Metabolite Profiling Facility, Purdue University
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 non-linear 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 non-invasive 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 widespread involvement of acrolein in human health, the benefits of this study have the potential to significantly enhance human health.
Emil Venere | EurekAlert!
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