Acrolein detection: potential theranostic utility in multiple sclerosis and spinal cord injury

Abstract

Oxidative stress has been implicated as a major pathological process underlying CNS disease and trauma. More specifically, acrolein, an unsaturated aldehyde, produced by way of lipid peroxidation, has been shown to play a crucial role in initiating and perpetuating detrimental effects associated with multiple sclerosis and spinal cord injury. In light of these findings, quantification of acrolein levels both systemically and locally could allow for the use of acrolein as a biomarker to aid in diagnosis and guide treatment regimens. The three main approaches currently available are acrolein derivatization followed by LC/GC–MS, application of an acrolein antibody and subsequent immunoblotting, and the 3-hydroxypropylmercapturic acid-based method. Of these three strategies, the 3-hydroxypropylmercapturic acid-based method is the least invasive allowing for rapid translation of acrolein detection into a clinical setting.

Keywords::

• 3-HMPA
• acrolein
• acrolein–lysine adduct
• hydralazine
• multiple sclerosis
• oxidative stress
• spinal cord injury

Financial & competing interests disclosure

This study was supported by the Indiana State Department of Health (Grant #204200 to R Shi), National Institutes of Health (Grant #NS073636 to R Shi) and Indiana CTSI Collaboration in Biomedical Translational Research (CBR/CTR) Pilot Program Grant (Grant #RR025761 to R Shi). There is no conflict of interest for any of the authors. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Acrolein, a byproduct of oxidative stress, is a key mediator of CNS pathologies and is capable of eliciting neuronal membrane damage, demyelination and mitochondrial dysfunction.

• Acrolein was found to be present at increased levels following spinal cord trauma and corresponded with behavioral deficit.

• Experimental autoimmune encephalomyelitis mice exhibited elevated levels of acrolein locally and systemically, which corresponded with the behavioral score.

• Attenuation of acrolein toxicity using hydralazine offered neuroprotection in spinal cord injury and experimental autoimmune encephalomyelitis animals.

• Detection of acrolein levels allows for the potential use of acrolein as a biomarker.

• Acrolein derivatization and subsequent use of LC/GC–MS is a well-characterized method and has been used in many studies.

• Immunoblotting techniques, which utilize an acrolein antibody, offer high sensitivity and allow the investigator to quantify acrolein levels locally; however, due to the highly invasive nature of this technique, clinical applications are limited.

• Quantification of 3-hydroxypropylmercapturic acid, an acrolein metabolite, allows for the measurement of systemic acrolein levels from a urine sample, rendering it highly applicable clinically.