Oxygen can be a tricky and deceptive ally to have. There is a plethora of medical evidence that points towards the fact that oxidative stress can cause damage to your cells and tissues. Despite this, the free radicals that are created as a result of oxidative stress also occur during a normal metabolism and as a result contribute to variations in a human being’s health as well as to the inception of disease. Free radicals can be thought of as molecules with an odd number of electrons. The odd or unpaired electron is very reactive because it proactive searches to pair with another free electron. Free radicals are created when a human being’s metabolism is in an oxidative state and is producing energy. Free radicals contribute to things such as:
- Enzyme-catalyzed reactions
- Electron transport in mitochondria
- Signal transduction and gene expression
- Activation of nuclear transcription factors
- Oxidative injury to molecules, cells and tissues
- Antimicrobial action of neutrophils and macrophages
- Aging and disease
Normal metabolisms need oxygen to function, which is a free radical itself. Scientists assume that due to evolution, oxygen was chosen as the terminal electron acceptor for respiration. Oxygen is biradical as two unpaired electrons of oxygen spin in the same direction, and therefore not as dangerous as some other free radicals. Other varieties of oxygen-derived free radicals including superoxide and hydroxyl radicals, that are generated during metabolism or via ionizing radiation are more powerful oxidants and as a result can be more dangerous.
On top of the studies conducted on the biological effects of these particular reactive oxygen variants, studies on reactive nitrogen variants has been gradually increasing over the years. NO, or nitrogen monoxide (nitric oxide), is a free radical created by NO synthase (NOS). This enzyme modulates physiological reactions such as vasodilation or producing signals in the brain. When the body is experiencing inflammation, on the other hand, NOS or iNOS synthesis is induced. The iNOS contributes to an overproduction in NO, which results in injury. Even of more concern is that excessive amounts of NO can react with superoxide to generate the highly toxic product peroxynitrite. Oxidation of lipids, proteins and DNA can happen, which contributes to a higher risk in tissue damage.
Reactive oxygen as well as nitrogen variants are contributors to the process of normal cell regulation where it’s imperative for signal transduction to function properly using oxidants and redox status. The signaling cascade contributing to inflammatory reactions are derived from oxidative stress being a critical upstream factor, through their stimulation of adhesion molecules and chemoattractant production. When hydrogen peroxide is broken down to generate hydroxyl radicals, the transcription factor for the simulation of inflammatory reactions, NF-kB, might also be mobilized. The excessive production of these responsive variants is poisonous, secreting cytostatic effects, resulting in membrane injuries, and mobilizing the pathways of cell death, which includes apoptosis and necrosis.
Research has shown that all diseases include the presence of some form of free radicals. The majority of these diseases have free radicals as a secondary cause in addition to the primary disease process, but for some diseases free radicals seem to be the primary cause. From this we can extrapolate the existence of a thin red line that divides the usefulness and impact on health and disease of oxidants and antioxidants. In order to guarantee some degree of a healthy aging experience, the balance between these must be maintained.
Oxidative stress as a medical terminology implies the antioxidant status of cells and tissues is changed by their contact with oxidants. As a result, the redox status is impacted by how much a cell’s components are in an oxidized state of being. Generally speaking, there is a reducing environment inside cells that act as a shield against the startup of the process of oxidative damage. Protein misfolding or aggregation is not allowed as the reducing environment contains disulfide bonds (S-S) that do not spontaneously generate as sulfhydryl groups are kept in a reduced state (SH). The reducing environment is sustained by the process of oxidative metabolism and by the activities of antioxidant enzymes and substances, among them glutathione, thioredoxin, vitamins E and C, and enzymes such as superoxide dismutase (SOD), catalase and the selenium-dependent glutathione and thierodoxin hydroperoxidases, whose purpose is to clear away reactive oxygen variants.
Alterations in the redox status and the decrease of antioxidants happen throughout oxidative stress. The thiol redox status can be an effective index to go by as it pertains to oxidative stress mostly due to the fact that metabolism and NADPH-dependent enzymes sustain cell glutathione (GSH) almost entirely in its reduced state of being. Oxidized glutathione, also known as glutathione disulfide or GSSG, collects under conditions of having been in contact with oxidants, and this alters the ratio of oxidized to reduced glutathione. An increase in this ratio points towards the presence of oxidative stress. A lot of tissues are comprised of hefty amounts of glutathione, 2-4 mM in erythrocytes or neural tissues and up to mM in hepatic tissues. Reactive variants of oxygen and nitrogen can be directly impacted by glutathione to decrease the levels of this substance, the cell’s foremost preventative antioxidant.
The current consensus among medical researchers is that the decrease of oxidative stress can contribute to improvements on a clinical level. Free radicals can be produced in excessive amounts, or the natural antioxidant system defenses can falter, initially commencing the process of oxidative status, and then eventually metamorphing into oxidative damage and illness. Two diseases that result from this oxidative stress are cancer and heart disease. Oxidation of low density lipoproteins in human beings is regarded as the first phase towards the progression and gradual development of atherosclerosis, which is the precursor to cardiovascular disease. Injury to the DNA as a result from oxidation jump starts the process of carcinogenesis.
Convincing support for the contribution of free radicals to the development of diseases is derived from epidemiological research that presents a strengthened antioxidant status is connected to a reduced risk of a number of diseases. Vitamin E leading to the stalling of the development of cardiovascular disease is one that comes to mind. An enhanced antioxidant status is also connected to a smaller risk of cataracts and cancer, and some recent studies indicate an inverse correlation between antioxidant status and the manifestation of rheumatoid arthritis and diabetes mellatus. Alas, the number of implications where antioxidants can be effective in the prevention and treatment of an illness is on the rise.
Oxidative stress nonetheless remains a secondary cause for most diseases instead of a primary cause. Some diseases that are primarily caused by oxidative stress include inflammatory bowel disease, retinal ischemia, cardiovascular disease and restenosis, AIDS, ARDS and neurodegenerative diseases such as a stroke, Parkinson’s disease and Alzheimer’s disease. These implications might provide evidence sufficient enough to suggest antioxidant treatment is feasible as there is a clear contribution of oxidative stress to oxidative damage in these diseases.
In these series of articles we will explore oxidative stress and it’s impact on the many illness that can be harmful to our organ systems by highlighting empirical evidence and medical benefits of applying this knowledge. These series of articles will also concentrate on crucial natural antioxidant enzymes and antioxidant substances that encompass vitamins A, E and C, flavonoids, polyphenols, carotenoids, lipoic acid, among other nutrients that can be found in various foods and drinks. Oxidative stress can be detrimental to the maintenance of human health. There is an increasing body of literature that presents evidence pointing in the direction of the conclusion that a balance between oxidants and antioxidants is required for the long term sustainability of human health and the prevention of pathological responses that lead to the development of illnesses. These series of articles is available for all to read but is primarily focused on informing researchers in biomedical sciences and clinicians. The fact that we can undoubtedly provide ourselves and our patients with the ability to age in a healthy and sustainable manner requires knowledge regarding how oxidants and antioxidants can positively or adversely affect biological systems.