Reactive oxygen species (ROS) are widely believed to cause or aggravate several human pathologies such as neurodegenerative diseases, cancer, stroke and many other ailments. Antioxidants counteract the harmful effects of ROS and therefore prevent or treat oxidative stress-related diseases.
The immune response depends on intracellular oxidation-reduction (redox) reactions. Redox active molecules fulfill key functions in immunity. Redox reactions trigger and shape the immune response. Regulatory mechanisms provided by redox-activated signaling events guarantee the correct proceeding of immunological processes. However, redox-active (free radical) molecules can be harmful to healthy host cells as well as to pathogens. Continued imbalances in redox homeostasis eventually lead to crucial failures of control mechanisms. It’s well accepted that a build-up of free radicals leads to unchecked inflammation and various immune-related concerns. Maintaining a balance between free-radical and antioxidant activity inside the cells is crucial.
Free radicals are generated in initiating and sustaining the active immune response and antioxidants are needed and used in greater volume than under normal conditions. Research literature continues to validate the benefits of moderate antioxidant supplementation, especially for supporting the immune system. Antioxidant nutrients, like selenium, zinc and vitamins A, C, D, and E, synergize to support redox balance. Glutathione is a potent cellular antioxidant, and N-acetylcysteine (NAC) is its rate-limiting precursor so supplementation with glutathione or glutathione precursors is an additional strategy.
Glutathione (GSH) is often referred to as the body's master antioxidant. Composted of three amino acids - cysteine, glycine, and glutamate - glutathione can be found in virtually every cell of the human body. The highest concentration of glutathione is in the liver, making it critical in the body's detoxification process. Glutathione is also an essential component to the body's natural defense system. Viruses, bacteria, heavy metal toxicity, radiation, certain medications, and even the normal process of aging can all cause free-radical damage to healthy cells and deplete glutathione.
GSH is an extremely important cell protectant. It directly quenches reactive hydroxyl free radicals, other oxygen-centered free radicals, and radical centers on DNA and other biomolecules. GSH is a primary protectant of skin, lens, cornea, and retina against radiation damage and other biochemical foundations of P450 detoxification in the liver, kidneys, lungs, intestinal, epithelia and other organs.
Vitamin C is a potent reducing agent, meaning that it readily donates electrons to recipient molecules. Related to this oxidation-reduction (redox) potential, two major functions of vitamin C are as an antioxidant and as an enzyme cofactor.
Vitamin C can protect indispensable molecules in the body, such as proteins, lipids (fats), carbohydrates, and nucleic acids (DNA and RNA), from damage by free radicals and reactive oxygen species (ROS) that are generated during normal metabolism, by active immune cells, and through exposure to toxins and pollutants (e.g., certain chemotherapy drugs and cigarette smoke). Vitamin C also participates in redox recycling of other important antioxidants; for example, vitamin C is known to regenerate vitamin E from its oxidized form.
Vitamin C’s role as a cofactor is also related to its redox potential. By maintaining enzyme-bound metals in their reduced forms, vitamin C assists mixed-function oxidases in the synthesis of several critical biomolecules. Symptoms of vitamin C deficiency, such as poor wound healing and lethargy, result from impairment of these enzymatic reactions and insufficient collagen, carnitine, and catecholamine synthesis
Acetylcysteine (AC) is an aminothiol and synthetic precursor of intracellular cysteine and GSH and is thus considered an important antioxidant . AC has been widely used as a research tool in the field of apoptosis research for investigating the role of Reactive oxygen species ROS in induction of apoptosis.
It is generally assumed that the action of AC results from its antioxidative or free radical scavenging property as an antioxidant through increasing intracellular GSH levels; however, AC also possesses a reducing property through its thiol-disulfide exchange activity. For example, AC has been shown to induce cell cycle arrest in hepatic stellate cells by modulating the mitogen-activating protein (MAPK) pathway.
Superoxide dismutases (SODs) are a group of metalloenzymes that are found in all kingdoms of life. SODs form the front line of defense against reactive oxygen species (ROS)-mediated injury. These proteins catalyze the dismutation of superoxide anion free radical (O2-) into molecular oxygen and hydrogen peroxide (H2O2) and decrease O2- level which damages the cells at excessive concentration. This reaction is accompanied by alternate oxidation-reduction of metal ions present in the active site of SODs. Based on the metal cofactors present in the active sites, SODs can be classified into four distinct groups, one of which is Copper-Zinc-SOD (Cu, Zn-SOD).
SODs constitute a very important antioxidant defense against oxidative stress in the body. Several studies have been performed that reveal the therapeutic potential and physiological importance of SOD. The enzyme can serve as an anti-inflammatory agent and can also prevent precancerous cell changes. Natural SOD levels in the body drop as the body ages and hence as one age, one becomes more prone to oxidative stress-related diseases.
Superoxide dismutase participates in a dismutation reaction in order to convert superoxide into the less toxic substances of hydrogen peroxide and dioxygen. A dismutation reaction is a reaction in which one substance is oxidized and the other is reduced simultaneously. There are two redox reactions that occur in the copper zinc superoxide dismutase system, and copper catalyzes these reactions. In one reaction Cu2+ is reduced to Cu1+, while the superoxide molecule, O2-, is oxidized to O2. In the second step Cu1+ is oxidized to Cu2+, while a second superoxide molecule is reduced to hydrogen peroxide, H2O2.