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Antioxidants and Their Significance in Preventing Disease and Oxidative Stress

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Normal cellular function continuously produces free radicals. If the body produces an excess of free radicals, it creates an atmosphere for disease. Antioxidants can help deter oxidative stress, which simultaneously prevents free radicals. Specifically, what is the significance of antioxidants, and how do they prevent disease and oxidative stress?

The First Line Defense Antioxidants

Antioxidants aid in the prevention of oxidation, delaying some types of cell damage. They protect cells against free radical molecules that are produced during digestion or when exposed to negative environment sources (i.e. pollution or tobacco smoke).

The body includes a complex antioxidant defense grid that relies on endogenous enzymatic and non-enzymatic antioxidants, acting at different levels. Together, these defense antioxidants fight against free radicals, supporting the resistance of damage and the effects to biomolecules and body tissue.1 There are four levels of defense antioxidants.

Bacteria are the most diverse organism, inhabiting all environments and evolving enzymes to mitigate cellular damage from potentially hazardous reactive oxygen species (ROS). Free radicals and other ROS are derived either from endogenous metabolic processes in the human body or from external sources.7

Antioxidants can safely react with free radicals to neutralize or terminate the chain reaction before vital molecules are damaged. Enzymatic systems exert defenses in a number of ways. The first line of defense includes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX), and may be the most important. These are fast acting antioxidants, suppressing or preventing the formation of free radicals or reactive species in cells.1

SOD is an enzyme that alternately catalyzes the dismutation (or partitioning) of the superoxide radical into ordinary molecular oxygen and hydroperoxide, acting as an important antioxidant in nearly all living cells exposed to oxygen.1 This enzyme requires a metal cofactor for its activity. The metal ions which are normally bound by SOD are iron (Fe), zinc (Zn), copper (Cu), and manganese (Mn).

Several tissues including the heart have been observed to possess the cellular resources to transcribe SOD3 mRNA from SOD DNA (1). This is important since SOD3 is the major enzymatic antioxidant defense against vascular and cardiovascular diseases.

CAT is a common antioxidant that converts hydrogen peroxide to oxygen and water in all living tissues. It uses either iron or manganese as a cofactor and is highly efficient at breaking down hydrogen peroxide molecules. 1

GPX is an important intracellular cytosolic enzyme catalyzing the reduction of hydrogen peroxide to water and oxygen, reducing peroxide radicals to alcohols and oxygen. 1 GPX has the capacity to scavenge free radicals.

Microbial Pathogens and Immunity

Like all organisms, pathogenic microbes produce ROS as byproducts of aerobic metabolism, but the burden of ROS is magnified when these microbes confront the oxidative burst of the host. 2 Macrophages and neutrophils attack invading microbes with toxic superoxide as part of the innate immune response. 2 To neutralize the attack, some microbial pathogens may express SODs since they are metalloenzymes – an enzyme containing a metal ion, functions like coenzymes and imparts activity to the enzymes.

As with other eukaryotes, pathogenic fungi express a largely cytosolic Cu/Zn SOD1 and a distinct Mn-containing SOD2 in the mitochondrial matrix.

Pathogenic microbes can cause certain types of infections or diseases. The roles of SOD in bacterial survival and pathogenesis vary depending on the species. Virulence factors are encoded in and translated from genes in chromosomal DNA, bacteriophage DNA, or plasmids of bacteria. 6

How does oxidative stress cause disease?

Free radicals can be formed naturally during normal metabolic processes, by the immune system responding to injury or infection, and environmentally through exposure to things like pollution. They are unstable as they possess a lone pair of electrons and become highly reactive. Vital cellular structures and functions can be lost, causing pathological conditions and triggering the production of oxidative stress.

The redox state of the cell is a dynamic balance between the number of antioxidants and free radicals in the body, acting like the voltage of a battery. If the redox fluctuates too high or low, the ‘battery’ doesn’t function properly. An imbalance causes the cells to prematurely age and become dysfunctional

Oxidative stress can contribute to chronic conditions like cancer, heart disease, diabetes, Alzheimer’s disease, Parkinson’s disease, and eye diseases such as cataracts and age-related macular degeneration. 4

Antioxidants work to neutralize and remove free radicals by donating an electron.  Here are some of the best way to get in antioxidants through food:

Resources

1) Ighodaro, O., Akinloye, O. (2017, November 13). First line defense antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defense grid. Retrieved April 27, 2020, from https://www.sciencedirect.com/science/article/pii/S2090506817301550

2) Broxton, C., & Culotta, V. (2016, January 7). SOD Enzymes and Microbial Pathogens: Surviving the Oxidative Storm of Infection. Retrieved April 27, 2020, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4712152/

3) Asakura, H. (2018). Antioxidants and Polyphenols in Inflammatory Bowel Disease: Ulcerative Colitis and Chrohn Disease. In T. Kitahora (Ed.), Polyphenols: Prevention and Treatment of Human Disease (Second ed., pp. 279-292). Academic Press. doi:https://www.sciencedirect.com/science/article/pii/B9780128130087000230?via%3Dihub

4) Antioxidants: In Depth. (n.d.). Retrieved from https://www.nccih.nih.gov/health/antioxidants-in-depth

5) Walker, A. (2014, September 29). The Human Microbiota and Pathogen Interactions. Retrieved April 29, 2020, from https://www.sciencedirect.com/science/article/pii/B9780123971692000196

6) Payne, S. (2017, September 01). Viral Pathogenesis. Retrieved April 29, 2020, from https://www.sciencedirect.com/science/article/pii/B978012803109400009X

7) Hajhashemi, V., Vaseghi, G., Pourfarzam, M., & Abdollahi, A. (2010, January). Are antioxidants helpful for disease prevention? Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3093095/

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