Health Happening
The "No-Brainers" for Physical and Mental Health:
| Sources of ROS | ||
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| Cellular Metabolism | Immune System Cells | Hyperglycemia |
| Irradiation | Excessive metals | Damaged fats |
| Smoke, smoking | Food Additives | Wearing synthetics |
| Caffeine | Cell phones | Non-fresh food |
| Radiation | Too much oxygen | Micro-waved food |
| TV screens | Deep-fried foods | High voltage cables |
| Smoke, smoking | Food Additives | Wearing synthetics |
| Bio-oxidative Therapies | Herbicides, pesticides | Environmental pollutants |
| Drugs, vaccinations | Psychological stress | Physical Trauma |
ROSare a by-product of Aerobic cellular energy production - ROSare produced in the body as a by-product when oxygen is used to produce energy from food components. As part of this process, ROSare formed as oxygen is chemically reduced along the electron transport chain (ETC) in the mitochondria (this accounts for 90% of cell's oxygen consumption).
ROSare leaked from the Electron Transport Chain (ETC). Both the mitochondria and endoplasmic reticulum leak a considerable number of superoxide radicalsgenerated from molecular oxygen, which under normal circumstances, is by far the main source of radicals that the body must deal with.
| Coenzyme Q generates superoxide (O2•-) |
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- One of the major sites of O2 • - generation is the ETC which leaks ROS radicals in the form of semiquinone radicals of coenzyme Q. The 1-electron form of CoQ occasionally leaks into the inner mitochondrial membrane. The nonspecific interaction of a CoQH • with molecular oxygen results in the formation of a O2•-which abstracts an electron from some other molecule and initiates a free radical chain reaction. |
By electron transfer reactions in body (both enzymatically and non-enzymatically mediated
Red blood cells produce ROS during the binding and release of oxygen and carbon dioxide by hemoglobin.
The immune system white blood cells produce ROS when body reacts to an adverse factor. E.g. A wound, fever, nervous imbalance (stress), microbial infection or toxin. These conditions precipitate an inflammatory response, in whichradicals, ROS, RNS or other reactive oxidantsare released by immune system white blood cells (E.g. macrophages).
Emotional Stress creates free radicals. Possibly today's main oxidation-causing stressor.
- Histamine is produced as a result of Erratic Stress - Accumulating histamineleads to inflammation and plaque formation.(Bruce H. Lipton's histamine theory is that erratic stressinduces mast cells on blood vessel endothelium to emit histamine, which causes cells to multiply).
- Having a Type-A personality is linked to an increased risk of CHD. Characteristics include time urgency and competitiveness.
Infectious Microbes such as bacteria, viruses, protozoa initiate an inflammatory process that leads to increased ROS production by phagocytes. E.g. infectious bacteria Chlamydia pneumoniae and the Herpes simplex virus have been proposed as initial inflammatory infectious agents in atherosclerosis.
- Phagocytes deliberately produce ROS to remove microbes. An infection in the body will cause this immune system attack force to "burst"into action. Circulating, small white blood cells (WBCs), called neutrophils, are "Johnny-on-the-spots", signalled by prostaglandins and histamine, quickly "squeezing"through the capillary walls and engulfing and destroying bacteria and fungi. Later, large WBC monocytes circulating in the blood stream enter the invaded tissues, where they develop into macrophages (meaning "big-eaters"). Macrophages "gobble up"invading bacteria, fungi, parasites and dead neutrophils. The process of engulfing, encapsulating and "eating"microbes is called PHAGOCYTOSIS. Additionally, there is some leakage of Superoxide (O2 •- ), H2O2 & other ROS at the interface of the bacterium and the activated phagocyte
Babior, B. M. Oxygen-dependent microbial killing by phagocytes (first of two parts)(1978) N. Engl. J. Med. 298, 659-668.
- ROS are released in the synthesis of prostaglandins and leukotrienes. Local "messenger" molecules released from unsaturated fatty acids, produced in response to trauma.
- Phagocytes are attracted to an injury site, where they remove damaged cells and promote healing. Phagocytes stimulate cellular proliferation of neighboring healthy cells. (These hormone-like mediators operate in localized tissues, regulating effects such as inflammation activity, smooth muscle contraction and dilatation, body temperature, and certain hormone functions).
Environmental toxins induce inflammatory response leading to damaging ROS and RNS. E.g. cigarette smoking by-products, exhaust fumes, household chemicals, heavy metals, pesticides/herbicides, certain drugs, radiation Pope et al. 2004; Suwa et al. 2002
- High Energy Exposure. E.g. ionising radiation, ultraviolet light, other forms of high energy. Radiation therapy may cause tissue injury due to ROS. Electromagnetic radiation (X rays, gamma rays) and radiation particles (electrons, photons, neutrons, alpha and beta particles) generate primary radicals by transferring their energy to cellular components such as water. These primary radicals can undergo secondary reactions with dissolved oxygen or cellular solutes.
- Tobacco smoke. Oxidants in tobacco exist in sufficient amounts to play a major role in injuring the respiratory tract and severely deplete intracellular antioxidants in the lung cells.
| SOME MORE DETAILS ON TOBACCO SMOKE |
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• Smoke oxidants include: aldehydes, epoxides, peroxides, and other free radicals, which may survive long enough to cause damage to the alveoli. • Present In the gas phase are: Nitric oxide, peroxyl radicals and carbon-centered radicals . • Relatively stable radicals are in the tar phase - including derivatives from various quinones and hydroquinones. • Micro-haemorrhages most likely are the source of iron deposition found in smokers' lung tissue - leading to the formation of OH• from H2O2. Smokers have elevated amounts of neutrophils in the lower respiratory tract possibly contributing to even more ROS. |
- Inorganic particles. Inhalation of inorganic particles (e.g. asbestos, quartz, silica) can lead to lung injury resulting in WBC production of damaging ROS. Asbestos inhalation has been linked to an increased risk of developing pulmonary fibrosis (asbestosis), mesothelioma and bronchogenic carcinoma. Silica particles and asbestos are phagocytosed by pulmonary macrophages. These cells then rupture, releasing proteolytic enzymes and chemotactic mediators causing infiltration by other cells such as neutrophils. This initiates an inflammatory process that leads to increased ROS production. Phagocytes release ROS into ECM, damaging surrounding tissues.
- Drugs. A number of drugs increase the ROS production, acting additively with hyperoxia (excess oxygen) to accelerate the rate of damage. These drugs include antibiotics, antineoplastic agents (E.g.bleomycin), anthracyclines (adriamycin) and methotrexate.
Hyperglycemia (chronically high blood sugar levels) induces oxidative stress in endothelial cells, which can cause an increase in the production of ROS (reactive oxidants, includes free radicals)
Ceriello P et al, High Glucose Induces Antioxidant Enzymes in Human Endothelial Cells in Culture, Diabetes Vol 45 April 1996.
Hyperglycemia increases the formation of oxidized LDL. An important modulator in atherosclerosis and cardiovascular death.
Why the hyperglycemia?
• Excess dietary sugars and refined carbohydrates increases blood glucose - usually accompanied by prolonged high insulin levels.
• Excess consumption of high fructose corn syrup in processed foods
• INSULIN resistance as in Type 2 diabetes further increases blood sugar;
Organs and tissues NOT dependent on INSULIN for their absorption of glucose are more susceptible to damage from periods of hyperglycemia than other organs. i.e. kidneys, blood vessels, peripheral nerves and lenses of the eye.
ROS are formed as necessary intermediates in a variety of enzymatic reactions
ROS are involved in intercellular and intracellular signaling. E.g. addition of superoxide or hydrogen peroxide to a variety of cultured cells leads to an increased rate of DNA replication and cell proliferation.
ROS production increased by EXERCISE / Some health problems. ROSproduction is higher during intensive physical exercise and with certain diseases such asdiabetes.
- In fried, cooked, cured, aged, or processed foods, chiefly meats, eggs and dairy. E.g. powdered eggs/milk, scrambled eggs. Dietary oxidized cholesterol is equally distributed to both HDL and LDL in the body [University of California Study published Feb. 1, 2003].
- Cholesterol produced by the body or consumed in food is oxidized in the body. in its antioxidant role when it comes into contact with free radicals. (lipid peroxidation induced by ROS/RNS seems to be involved not only in cardiovascular disease, but also in cancer, rheumatoid arthritis, and other degenerative health problems, including accelerated aging).
Oxidized Polyunsaturated,Omega-6and Omega-3 Fats. These "essential" fats are easily oxidized by ROS and RNS to become cell-damaging lipid peroxides. They are produced:
- In food before consumption. E.g.during the usual high-temperature commercial process of extracting vegetable oils from seeds, or in high-temperature processed foods. E.g. fried foods.Dietaryomega-3and omega-6fats are essential to well-being, but need to be consumed undamaged, in balance, together with fat-protective antioxidants, such as vitamins A, D, E. and K;
- In the body after consumption. When antioxidants are deficient;particularly damaging to cell membranes;
- 2005 study of 700 nurses. Found that those consuming the most trans fats had a significantly higher risk of cardiovascular disease. Link to nurses study
- Increase both LDL and Lp(a). One study showed significant increases in Lp(a) levels of subjects consuming diets high in trans fats, but not in those consuming high levels of saturated fats (J. Lipid Res). Nutritionist/author Dr. Mary Enig maintains that saturated fats actually LOWER Lp(a) levels.
- Decrease HDL.
Ozone therapy, hydrogen peroxide therapy and PDT. Deliberately introduce controlled amounts of ROS into the body.
J Lipid Res 1992 Oct;33(10):1493-501
| PHAGOCYTOSIS in MORE DETAIL | ||||
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During phagocytosis, phagocytic cell membrane enzymes (e.g flavoprotein cytochrome-b-245 NADPH oxidase enzyme system) are activated by exposure to:
to initiate a respiratory burst at the cell membrane, consuming large amounts of oxygen to produce Superoxide (O2 •- ) . H2O2is then formed from O2 • - by dismutation, with subsequent generation of OH• and HOCl by bacteria Rosen H, Rikata R, Waltersdorph AM, Klebanoff S; 1987 H2O2 and O2 • - are not reactive enough to destroy microbes themselves, and must be converted to OH•, 1O2* , HOCl or other oxidizing agent. However, the slow reactivity of H2O2 allows it to survive long enough to diffuse through microbial membranes and react with their lipids or DNA. Ozone (O3) is produced by antibody-catalyzed production of trioxidane from water and neutrophil-produced 1O2* |
