Free Radicals Can Wreak Havoc in Our Bodies. Are Specialized Antioxidants the Key?
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You are probably familiar with the antioxidant Vitamin C, which we are supposed to consume for our health. But have you ever wondered why? Well, one of the main reasons is that antioxidants like Vitamin C are necessary to balance the activity of tiny substances called free radicals. If antioxidants aren’t consumed in sufficient quantity, through diet or supplementation, free radicals can become little troublemakers and cause all kinds of problems within our cells, especially within our body’s control center – the brain. Let's delve into the world of antioxidants, free radicals, and how they impact our brain health.
Dynamic Duos: Heroic Antioxidants and Misunderstood Free Radicals
Free radicals are unstable molecules that are produced naturally in our bodies. From this context, you might think that free radicals are bad, but that’s far from the truth. Among many beneficial roles, these molecules act as messengers to help your body’s cells communicate with each other, and they also play a very important role in the immune response to illness or injury.
When free radicals accumulate in our bodies, however, a process called “oxidative stress” occurs; this refers to a high amount of free radicals with a low amount of antioxidants to counteract the free radical activity. The relationship between antioxidants and free radicals parallels that of a popular duo from the TV show Friends; like Janice, free radicals are quite turbulent and can leave a trail of destruction behind them, but antioxidants (akin to Chandler) can help restore order and a sense of stability.
If left unchecked, however, free radicals can cause significant damage to the cells in your body through oxidative stress. The effects of oxidative stress can damage cells throughout your body, including your brain cells. Over a lifetime of exposure to oxidative stress, this damage may add up and may lead to common neurological problems, including age-related cognitive decline, memory problems, and an increased risk of neurodegenerative diseases, such as Alzheimer's and Parkinson's disease. Fortunately, our bodies are equipped with an internal defense system to tackle oxidative stress: antioxidants.
Just as Chandler brings laughter and light to his friends, antioxidants bring balance and stability to our cellular environment; antioxidants protect our cells from the harmful effects of oxidative stress by neutralizing free radicals. Supplementing antioxidants or consuming a diet high in antioxidants, such as vitamins C and E, is essential for overall health and can certainly help reduce oxidative stress. While antioxidants can reach various parts of the body through the bloodstream, not all antioxidants are able to enter the brain because there is a tissue barrier that surrounds the brain and prevents many different kinds of molecules from entering it.
Thus, while it is important to consume a diet that is rich in antioxidants, to fight overproduced free radicals, we need to develop other ways to get antioxidants into areas of the body that might not be as accessible, such as the brain.
Catalase to the Rescue: A Real-Life Hero?
One powerful type of antioxidant which all living things produce (although leafy greens, like spinach and kale, contain higher levels of it) is called “catalase.” When oxidative stress is very bad, there might not be enough catalase production within the brain to fight the free radicals. Since catalase does not easily cross the brain’s protective tissue barrier, we need to develop other ways to get it into the brain.
In a recent study, researchers from the University of Western Ontario figured out a clever way of getting catalase into the brain: they packed a bunch of catalase molecules inside what’s called an “exosome”. Exosomes are essentially empty packages that the cells in your body use to share DNA, proteins, and other helpful molecules with each other; they are akin to the boxes that your Amazon orders are delivered in. What is special about these exosomes is that they can easily pass through the brain’s protective tissue barrier.
The researchers then performed some fancy chemical engineering that directs the exosomes to a very specific distribution hub within each cell, which is where the catalase molecules are normally produced and distributed to various parts of the cell. This process is analogous to how you purchase products from Amazon, which are shipped to a central distribution hub before being sent to your address. The researchers then repeatedly gave the packaged catalase to mice over a few weeks, allowing it to enter their brains. They were most interested in confirming that the catalase entered and spread across the brain, and whether there was any damage to the brain or other important organs not related to the brain (for example, the liver and the intestines) after treatment with the catalase.
They discovered that the catalase did indeed enter the brain and that there was no evidence of organ damage! When targeted antioxidants like catalase are used to increase antioxidant activity within the brain, we can amplify the brain's antioxidant defence system far beyond that of dietary intake or vitamin supplementation. The way that catalase was used in this study allows it to be redirected to the main antioxidant processing hubs within each cell to combat the harmful free radicals (and oxidative stress), which is believed will reduce the related risk of brain cell damage and the subsequent downstream consequences (such as memory loss and dementia).
Furthermore, by administering catalase in this way, the researchers would be able to alleviate the burden on a body's natural antioxidant systems, allowing the antioxidants that are naturally produced to be reallocated to other important cellular processes they are required to play (beyond fighting free radicals). This study is one of the first steps in a series of experiments and shows that exosome-packaged catalase is safe and reaches the brain! Eventually, researchers will use mouse models of disease (for example, mice that have Parkinson’s Disease-like pathology) to assess how effective this treatment is. Hopefully, one day, we will be able to use this method to treat brain disorders that are associated with oxidative stress in humans!
Original Article:
Hayes, S. H., Liu, Q., Selvakumaran, S., Haney, M. J., Batrakova, E. V., Allman, B. L., Walton, P. A., Kiser, P. & Whitehead, S. N. (2021). Brain targeting and toxicological assessment of the extracellular vesicle-packaged antioxidant catalase-SKL following intranasal administration in mice. Neurotoxicity Research, 39(5), 1418–1429. https://doi.org/10.1007/s12640-021-00390-6