Oxidative Stress
Radical atoms originating from molecular oxygen in cells are called reactive oxygen species (ROS). The body uses antioxidants to neutralize the effects of these ROS in the body. However, excess ROS in the body occurs induces oxidative stress because it overwhelms antioxidants’ protective effects, leading to cell and tissue damage in the body. In essence, oxidative stress stems from an unfavorable imbalance between ROS production and protective antioxidants, resulting in the damage of biomolecules, such as nucleic acids, proteins, and lipids. Usually, infection, trauma, heat injury, toxins, vigorous exercise, and hyperoxia trigger short-term oxidative stress.
The damaged tissues and cells generate ROS in excess amounts due to increased stimulation of enzymes, such as lipogeneses, xanthine oxidase, and cyclooxygenase. Moreover, the secretion of copper ions, release of free irons, activation of phagocytes, and interference of the electron transport chains contribute to excess ROS production. An imbalance between protective antioxidants and ROS in the body is associated with the occurrence, development, and progression of cancer. The extent of chemotherapy and radiation therapy’s side effects is also associated with the imbalance of antioxidants and ROS in the body. Additionally, excess ROS has a role in initiating and developing age-related eye diseases, Parkinson’s disease, and diabetes.
Oxidative Stress and Biomedical Conditions
Researchers have claimed that oxidative stress has numerous roles in numerous biomedical conditions, such as cancers, inflammation, and aging. Currently, oxidative stress has been linked to the genesis and progression of inflammatory diseases, including vasculitis, lupus erythematosus, arthritis, adult respiratory diseases syndrome, and glomerulonephritis. Oxidative stress is also associated with the occurrence of ischemic diseases such as stroke, heart diseases, intestinal ischemia, gastric ulcers, hemochromatosis, hypertension, smoking-related disorders, emphysema, hypertension, neurological disorders, alcoholism, and acquired immunodeficiency syndrome. The presence of ROS in excess causes oxidative stress in the body, leading to the oxidation of proteins and lipids and the transformation of their structures and roles in the body.
Role of Antioxidants on Carcinogenesis
The mechanism of carcinogenesis shows that nitrogen species and ROS, including hydrogen peroxide, superoxide anion, nitric oxide, hydroxyl radical, and their metabolites, contribute to cancer occurrence and progression. For instance, ROS causes DNA damage by breaking strands, modifying bases, and creating protein-DNA cross-linkages. Researchers have provided ample evidence to demonstrate that free radicals play a critical role in genetic material mutation, the transformation of cells, and carcinogenesis. In analyzing the mechanism of carcinogenesis, radiation induces mutagenesis by damaging DNA via heme oxygenase (HO).
Radiolysis produces radicals and other reactive species, which damage DNA indirectly or directly via HO. The mechanism of DNA damage by radicals occurs by adding double bonds on pyrimidine bases and the removal of hydrogen atoms from ribose sugar, initiating a chain of reactions in cells. Coupled with lipid peroxides, radical also causes the stimulation of carcinogens in the body. Cumulative effects like these trigger cell mutagenesis, change cellular functions, initiate carcinogenesis, and develop cancerous cells in the body.
Antioxidants employ various mechanisms to protect cells and tissues from oxidative stress. Direct scavenging of ROS is one mechanism that reduces their concentration in the body to levels that the normal cellular mechanism can process. Inhibiting cell proliferation and the generation of ROS is another mechanism. For instance, beta-carotene has a protective effect against cancer because its antioxidant properties neutralize the oxidative radicals that cause genetic damage. Moreover, beta-carotene has a photoprotective ability against ultraviolet radiation, preventing it from inducing radicals and causing cancer.
This mechanism suggests that immunity could enhance the protective effect of beta-carotene on cancer. Vitamin C is also another molecule that is important in the prevention of cancer. Possible mechanisms of vitamin C include improvement of the immune response, antioxidant effects, enhanced detoxification, and prevention of synthesis of nitrosamines.
As another important molecule, vitamin E has antioxidant effects, which increases immuno-competence by stimulating the production of T-lymphocytes, boosting cell-mediated response, enhancing resistance to bacterial infection, improving humoral antibody protection, blocking micro cell line formation, repairing damaged genetic material, and inhibiting mutagen formation. In this view, vitamin E plays a critical role in the prevention of cancer and initiation of carcinogenesis. The use of beta-carotene, vitamin C, and vitamin E has proved to have a diminishing effect on the risk of cardiac cancer.
Effects of Free Radicals on Aging
Although aging is a natural process, the human body constantly rejuvenates itself and prevents aging. Researchers have established that free radicals destroy cells and cause significant pathological transformations associated with aging. ROS’s existence in the body has been linked to high incidences of disorders and diseases coupled with the aging process. The analysis of the mechanism shows that aging stems from the buildup of molecular, cellular, and physiological products in the body. Researchers have demonstrated that free radicals’ oxidation to reduce their amounts and diminish the rate of their production slows down the aging process.
Antioxidants in some foods aid in slowing the aging process and preventing the occurrence of diseases among people. Since enhanced oxidative stress happens in the aging process, the use of antioxidants may alleviate the oxidative stress of ROS. Additional research has indicated that the optimal consumption of antioxidants leads to reduced free radicals and diminished oxidative stress, resulting in a slowed aging process. Overall, antioxidants improve the quality of life and increase the life span among individuals.
Protective Mechanisms of Antioxidants
Although antioxidants have numerous effects on the body, two main mechanisms exist. The first one entails a chain-breaking mechanism where antioxidants act as electron donors to free radicals in the body. The removal of secondary radicals (ROS/reactive nitrogen species) through terminating chain reaction is the second antioxidant mechanism. Other mechanisms of antioxidants involve metal ion chelation, gene expression, electron donation, and co-antioxidants.
Antioxidant Enzymes
Superoxide dismutases (SODs) comprise antioxidant enzymes that protect cells from oxidative stress from radicals. SODs constitute a collection of metalloenzymes offering front-line protection against ROS’s oxidative stress and its associated cellular damages in all organisms. These enzymes provide protective effects by catalyzing the breakdown of free radicals of superoxide anions into oxygen and hydrogen peroxide, which subsequently decreases the concentration of ROS in cells. The redox reaction of metal ions present in the cells follows these reactions of SODs. Depending on the nature and type of ions that exist in the active sites, SODs can be grouped as iron-SOD, copper-zinc-SOD, Nickel-SOD, and manganese-SOD. These different groups of SODs exist in varied organisms and dissimilar cellular sections.
As antioxidant enzymes, SODs play a critical role in the protection of the body against free radicals. Numerous studies have confirmed that SODs have physiological significance and therapeutic potential against oxidative stress. SODs act as an anti-inflammatory agent in their mechanism of action, which hinders the initiation and development of cancerous changes. As the SOD levels diminish with age, it increases susceptibility to illnesses related to oxidative stress. In the cosmetics industry, SODs are incorporated in skin-care products because they have anti-aging properties of reducing the damage caused by free radicals, hindering the formation of lines, wines, and spots. Moreover, SODs in skin-care products protect against ultraviolet light, enhance wound healing, relax scar tissue, and rejuvenate tissues.
Ample evidence shows that SODs are significant in the occurrence of numerous disorders. The occurrence of cystic fibrosis, malignant breast cancer, erythrocyte-related diseases, post-cholecystectomy, cancer, AIDS, lateral sclerosis, neural apoptosis, and nephrotic syndrome have some links with SODs. Additionally, other researchers have suggested a significant association between the occurrence of Alzheimer’s disease and the activity of SODs in the body. Other studies have established that SODs aid in the recovery of burns from mustard gas. SODs are effective enzymes used to treat inflammation and myocardial and cerebral ischemic injuries in diverse animal models.
The action mechanism shows that SODs are small molecules that catalyze antioxidants activity, resulting in the alleviation of oxidative stress. As synthetic compounds, SOD mimetics imitate the role of SODs in the conversion of oxygen radicals into hydrogen peroxide for catalase to neutralize them easily into water. Features that make SOD mimetics effective in protecting against oxidative stress are their minute sizes, comparable activity, and extended half-life than the native SODs. Researchers have attempted to utilize to synthesize SODs and use them as therapeutic agents for diseases stemming from ROS. Literature review shows that SODs have various therapeutic potentials in the treatment of oxidative stress.
Lipid Peroxidation
Lipid peroxidation is a metabolic process that occurs naturally in cells owing to oxidative stress. The process of lipid peroxidation entails initiation, proliferation, and termination. At the initiation phase, the activation of oxygen occurs and forms the rate-limiting step in the process of lipid peroxidation. Polyunsaturated fatty acids in plasma membranes are likely to undergo peroxidation and induce oxidative stress. In cellular biology, lipid peroxidation is an important mechanism that ROS uses to induce oxidative stress and influences the structure of functions of plasma membranes. A growing body of evidence has indicated that lipid peroxidation is not only a destructive process of oxidative stress.
New findings have indicated that initiators of lipid peroxidation, lipid hydroperoxides, and oxygenated products have a role in forming signal transduction cascade, regulation of cell proliferation, and control of cellular growth. Further findings have shown that ROS and lipid peroxidation activators and mediators of apoptosis are key in preventing carcinogenesis, clearance of virus-infected cells, and elimination of damaged cells.
Additional findings demonstrate that lipid peroxidation plays a role in the suppression of carcinogenesis and cancer growth. While some studies show that n-6 fatty acid linoleic acid enhances cancer progression, other studies demonstrate that n-6 fatty acids and n-3 fatty acids prevent the growth and development of cancerous cells. The interaction of products of lipid peroxidation from these forms of lipids has a protective effect against oxidative stress.
These findings are valid because there is a significant correlation between the degree of lipid peroxidation and tumor cells’ growth in the body. A plausible mechanism of these observations is that pro-oxidants suppress cancer growth while antioxidants eliminate cancerous cells. The extent of cancer elimination relates to the suppression of lipid peroxidation by antioxidants in cells.