Researchers from Perdue University have found that a medical test originally developed to measure a toxin found in tobacco smokers could be adapted to measure the same toxin in people with spinal cord injuries and multiple sclerosis.
The toxin the test detects is called acrolein, which is produced by the body after injuries are sustained by nerve cells. When the nerve cells are injured, a cascade effect happens, triggering biochemical events in the body that worsen the severity of the injury. There are already drugs available that reduce the amount of acrolein found in the body. The test could potentially be very useful as a non-invasive way to detect and measure acrolein, which could open the door to better treatment options.
“If the acrolein level is high, it needs to be reduced, and we already have effective acrolein removers to do so,” said Riyi Shi, professor of neuroscience and biomedical engineering in Purdue University’s Department of Basic Medical Sciences, School of Veterinary Medicine, who is working with Purdue’s Center for Paralysis Research and Weldon School of Biomedical Engineering. “Reducing or removing acrolein may lessen the severity of symptoms in people who have nerve damage, but there has not been a practical way to monitor acrolein levels in nervous system trauma and diseases.”
“Based on this method, it was revealed that acrolein is significantly elevated in smokers and decreases following the cessation of cigarette smoke,” Shi said. “However, such a method has not been widely used for conditions in which acrolein is elevated due to central nervous system damage or disease.”
“We wanted to see if higher levels of acrolein corresponds to greater severity of spinal cord injury, and the answer is yes,” said Shi, who is working with Bruce Cooper, director of the Metabolite Profiling Facility in the Bindley Bioscience Center of Purdue’s Discovery Park. “This means reducing acrolein may help to control symptoms.”
This test does not detect acrolein directly, but rather determines if a byproduct of acrolein, a metabolite chemical compound called N-acetyl-S-3-Hydroxypropylcysteine, or 3-HPMA is present.
“Acrolein is very volatile, so it doesn’t remain stable long enough to monitor, but one molecule of acrolein will make one molecule of 3-HPMA, which is very stable in urine,” Shi said.
Acrolein is damaging to mitochondria, the energy source of cells. In multiple sclerosis, acrolein compromises the myelin sheath that protects the nerve’s axon, and it has a possible role in other diseases, as well.
“Nervous system trauma and diseases are like many other illnesses: A disease-associated marker can be critical for making a diagnosis, a therapeutic selection and a treatment evaluation,” Shi said. “Therefore, determination of acrolein levels gives you more assurance that you have an intense biochemical imbalance and biochemical damage and that you should use an acrolein scavenger as a treatment. We used different levels of hydralazine to see if it causes a dose-dependent reduction of 3-HPMA and found that, in fact, it did. This shows that this method is capable of monitoring the decrease of acrolein through treatment with acrolein-removing medications.”
“Due to widespread involvement of acrolein in the body, the benefits of this study have the potential to significantly enhance human health,” Shi said. “For example, there is evidence that heightened levels of acrolein could diminish an individual’s ability to recover fully from stroke and cancer.”
The study was funded by the National Institutes of Health, and the research findings were published in the Journal of Neurotrauma.
Do you know a smoker with multiple sclerosis or spinal cord injury? What would you tell them about the connection between cigarette smoke, MS, and SCI?