Oxidative Stress and Disease
The results of many peer-reviewed studies have shown oxidative stress caused by free radicals to be one of the primary instigators of hundreds of diseases and ailments, including aging.
Oxidative Stress and Disease
Oxidative stress can cause tissue injury or even cell death, which can occur mainly by two mechanisms, necrosis and apoptosis (aging process).
Oxidative stress plays a role in inflammation, accelerates aging and contributes in a variety of degenerative conditions such as cardiovascular diseases, atherosclerosis, cancer, cataract, central nervous system disorders, Parkinson’s disease, Alzheimer’s disease, inflammatory bowel disease, rheumatoid arthritis, diabetes, respiratory diseases, autoimmune diseases, liver diseases, kidney diseases, skin conditions and AIDS.
Oxidative stress is the presence of reactive oxygen species (ROS) above the available antioxidant buffering capacity. ROS can damage proteins, lipids, and DNA, altering the organism’s structure and function.
Definition of Reactive Species
Most stable molecular species have the electrons in their outer orbital, arranged in pairs. Each electron of this pair has an opposite spin, which is essential to stabilize the molecules. A free radical is a molecule with one or more unpaired electrons in its outer orbital, which makes this species very unstable, and tends to react with other molecules to pair this electron and thereby generate more stable species.
Types of Reactive Species
The highly reactive molecules include Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS). Of these reactive molecules (•O2¯, •NO, •ONOO-) are the most widely studied species and play essential roles in diabetic cardiovascular complications. Superoxide (•O¯2) is produced by one-electron reduction of oxygen by different oxidases including dihydro nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, xanthine oxidase, cyclooxygenase as well as by the mitochondrial electron transport chain during normal oxidative phosphorylation which is essential for generating ATP.
Sources of Free Radicals
The human body is continuously exposed to potentially harmful oxidative stresses during a lifetime. These may arise from exogenous as well as endogenous sources:
- Endogenous Sources of ROS: The primary source of ROS in vivo is aerobic respiration. ROS are also produced by peroxisomal β-oxidation of fatty acids, microsomal cytochrome P450 metabolism of xenobiotic compounds, stimulation of phagocytosis by pathogens or lipopolysaccharides, arginine metabolism and tissue-specific enzymes.
- Exogenous Sources of ROS: Excessive levels of free radicals are produced from pollution exposure; toxin exposure, including exotoxins such as heavy metals like mercury, lead, and cadmium. Different exotoxins include anticancer drugs, anesthetics, and analgesics. Toxin exposure also includes endotoxins such as those produced from bacteria, yeast, viruses, and parasites; trauma; radiation; electromagnetic fields; alcohol; cigarette smoke; medications; stress; allergens; cold; excessive exercise; dietary factors such as excess sugar, saturated fat and fried oils; malnutrition and various disease states.
Physiological Functions of Free Radicals
Free radicals, especially those centered on oxygen, have distinct functions and play a pivotal role in many physiologic reactions, as catalytic oxidation of some endogenous compounds and xenobiotics. Furthermore, they are significant participants in the regulation of smooth muscle tone and bacterial function of phagocytes.
Biological Actions of Free Radicals
Oxidative stress can cause damage to all molecular targets; DNA, proteins, and lipids. Often, it is not clear, which is the first point of attack, since injury mechanisms overlap widely. The primary cellular target of OS can vary; DNA is an essential early target of damage.
Oxidative Lipid Damage
Although lipid peroxidation (LP) affects many cellular components, the primary action sites involve membrane-associated polyunsaturated fatty acids (PUFA). Peroxidation of membrane-associated fatty acids and cholesterol will alter cell membrane fluidity and permeability characteristics and may eventually induce widespread membrane damage.
Lipid peroxides arising as a consequence of tissue damage can propagate further LP locally and at sites distant to areas of initial damage. The lipid peroxidation chain can lead to an increased steady-state concentration of lipid peroxides at the expense of oxygen and unsaturated lipids.
Further decomposition of peroxidized lipids yields a wide variety of end products, including (MDA) which is used as a marker of free radical-mediated reactions. LP can damage membrane proteins and lipids. Hydro-peroxides are stable products formed during the peroxidation of unsaturated lipids such as fatty acids and cholesterol.
Oxidative DNA Damage
Oxygen derived radicals may directly attack DNA, either the sugar, phosphate or purine and pyrimidine bases. On the other hand, oxidative DNA damage may be indirect through the rise of intracellular Ca++ ions. Free radical-mediated reactions can cause structural alterations in DNA (e.g., nicking, base-pair mutations, rearrangement, deletions, insertions, and sequence amplification). Degradation of the bases will produce numerous products, including 8-OH-Gua, hydroxyethyl urea, urea, thymine glycol; thymine and adenine ring-opened and saturated products.
Oxidative Protein Damage
Free radical injury results in inactivation and denaturation of essential proteins, the most at risk proteins are those with amino acids containing sulfur (methionine and cysteine), such as some enzymes and membrane ion transporters. The radical abstracts a proton and thereby oxidizes the sulphydryl moiety. The enzymes at risk include alpha-1 antiprotease, calmodulin, calcium ATPase, glucose-6phosphate dehydrogenase, and glyceraldehydes-3phosphate dehydrogenase.
Cellular Defenses Against Oxidative Stress
Cells manifest potent antioxidant defenses against ROS, including detoxifying enzymes and exogenous free radical scavengers (vitamins). The major enzymes that convert ROS to less reactive molecules are superoxide dismutase, catalase and glutathione peroxidase.
In healthy individuals, antioxidants form the body’s primary defense against ROS. They scavenge ROS before they cause damage to various biological molecules and prevent oxidative damage from spreading, by interrupting the free radical chain reaction. Antioxidants donate an electron to the free radical. Fruits and vegetables are the principal dietary contributors of antioxidants, being particularly rich in vitamins (A, C, E), oligo-elements, and polyphenols.
These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. The content on this website is not medical advice, and is intended for informational and educational purposes only.