Oxidative stress plays a major role in many chronic diseases affecting the modern world including: ALS, Alzheimer’s, cardiovascular disease, autism, and asthma. Oxidative stress is the imbalance between the anti-oxidant systems of the body and the levels of reactive oxygen species in the body. Reactive oxygen species (ROS) are molecules that contain oxygen and are highly reactive. They can attack and damage all parts of the cell including the DNA, cell membranes, and proteins. This damage in turn can cause inflammation which in turn can generate more ROS. Examples of ROS include hydrogen peroxide, superoxide, and peroxide. ROS are generated by our cells in day to day life but these are generally taken care of by anti-oxidants. ROS can also be generated by exposure to pollution, cigarette smoke, excessive inflammation, and toxins/chemicals. Diseases can develop or become worse when these ROs are not taken care of. One of the most studied anti-oxidants in the human body is glutathione, a small protein made up of three amino acids. Dysfunction in the glutathione system is associated with many diseases including cardiac damage and heart failure. Doctors can track the levels of glutathione in the blood as a way to monitor disease, however glutathione is not always readily present in the blood compared to the cells and so presents problems with detecting it. While searching for new ways to diagnose and treat heart failure, a group of researchers from Japan stumbled upon an amino acid that seems to act as a marker of oxidative stress and is able to promote the production of the glutathione anti-oxidant system.
The amino acid, 2-aminobutyric acid (2-AB), was shown to be elevated in patients who had a hole in two chambers of their heart. When this hole was repaired, the levels of 2-AB decreased. This would mirror the predicted fall in oxidative stress following the surgery. Second, the researchers were able to identify that 2-AB is made when glutathione is produced by the body during times of oxidative stress. In this regard 2-AB could be used as a biomarker for early detection of oxidative stress.
Interestingly, when the researchers put 2-AB on cardiac cells they saw an increase in glutathione levels within the cell. This indicated that 2-AB could be used to boost the anti-oxidant capacities of the cells. Best of all, when the researchers gave 2-AB to mice in their food they were protected from cardiac dysfunction caused by a common chemotherapeutic, doxorubicin. In these mice the 2-AB was able to increase the glutathione levels in the blood and heart by 20-50%.
These results have huge implications for the treatment of diseases with excessive oxidative stress. First, as a biomarker of ROS, 2-AB could help doctors better identify problems controlling oxidative stress and prevent possible exacerbations of disease. Second, 2-AB is a naturally occurring amino-acid found in some foods and so as a treatment for raising anti-oxidant levels it holds promise in human clinical trials. Additionally, the fact that this amino acid could prevent heart damage caused by doxorubicin means it may be useful in managing the side effects of this cancer therapy.
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