Heal Yourself At Home
DIY SOLUTIONS FOR YOUR HEALTH
Where do reactive oxygen species (ROS) come from in body?

Where do Body's ROS COME From?

ŸCellular Metabolism

ŸImmune System Cells

Ÿ Hyperglycemia

Ÿ Irradiation

ŸExcessive metals

ŸDamaged fats

ŸSmoke, smoking

ŸFood Additives

ŸWearing synthetics

ŸCaffeine

ŸCell phones

ŸNon-fresh food

ŸRadiation

ŸToo much oxygen

Ÿ Micro-waved food

ŸTV screens

ŸDeep-fried foods

ŸHigh voltage cables

ŸSmoke, smoking

ŸFood Additives

ŸWearing synthetics

Ÿ Bio-oxidative Therapies

Ÿ Herbicides, pesticides

Ÿ Environmental pollutants

ŸDrugs, vaccinations

Ÿ Psychological stress

ŸPhysical Trauma

(1) ROS are produced in the body in day-to-day life

(2) ROS can be directly introduced into the body

(1)ROS are produced in the body in day-to-day life

∞Metabolism (synthesis of energy) / Respiration∞

ROS are a by-product of Aerobic cellular energy production - ROS are produced in the body as a by-product when oxygen is used to produce energy from food components. As part of this process, ROS are formed as oxygen is chemically reduced along the electron transport chain (ETC) in the mitochondria (this accounts for 90% of cell's oxygen consumption).

Coenzyme Qgenerates superoxide (O2 -- )

- 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.

Electron leakage from Electron Transport Chains - Both the mitochondria and endoplasmic reticulum leak a considerable number of superoxide radicals generated from molecular oxygen, which under normal circumstances, is by far the main source of radicals that the body must deal with.

By electron transfer reactions in body - enzymatically or non-enzymatically mediated

∞ROS Produced by Red Blood Cells ∞

Red blood cells produce ROS during the binding and release of oxygen and carbon dioxide by hemoglobin.

∞ROS Produced by WHITE Blood Cells ∞

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 which radicals, ROS, RNS or other reactive oxidants are 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 histamine leads to inflammation and plaque formation. (Bruce H. Lipton's histamine theory is that erratic stress induces 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.

PHAGOCYTOSIS in More Detail

Physical Trauma

–   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 - by stimulating 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 – such as 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

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 damagingROS. 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.

∞ROS Produced by HYPERGLYCEMIA∞

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 Produced by OTHER BODY PROCESSES ∞

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 - ROS production is higher during intensive physical exercise and with certain diseases such as diabetes.

(2)ROS can be directly introduced into the body

∞ROS in oxidized (i.e. Damaged)Lipids (E.g. Trans Fats)∞

Oxidized Cholesterol

–   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-6 and 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.Dietary omega-3 and omega-6 fats 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;

Trans Fats

–   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 1992 Oct;33(10):1493-501 Nutritionist/author Dr. Mary Enig maintains that saturated fats actually LOWER Lp(a) levels.

–   Decrease HDL.

Damaged/Altered/Toxic Fats

∞HEALING THERAPIES∞

Healing therapies - Ozone therapy, hydrogen peroxide therapy and PDT deliberately introduce controlled amounts of ROS into the body.

PHAGOCYTOSIS in MORE DETAIL

During phagocytosis, phagocytic cell membrane enzymes (e.g flavoprotein cytochrome-b-245 NADPH oxidase enzyme system) are activated by exposure to:

Immunoglobulin-coated bacteria

Complement 5a

Immune complexes

Leukotriene

to initiate a respiratory burst at the cell membrane, consuming large amounts of oxygen to produce Superoxide (O2 - ) . H2O2 is 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*

AOX - ROS Related Links

ANTIOXIDANT / OXIDANT BALANCE Related Links

Health is a Balancing Act Between OXIDANTS and ANTIOXIDANTS

-A Powerful bioxidative tool

- LIFE'S OXYGEN PARADOX

- Meet Dr. ROS Jeckyll

and Mr. ROS Hyde

Dr. ROS Jeckyll

Mr. ROS Hyde

- Where do Body's ROS Come From?

Ÿ ROS Chart

- Antioxidants - Oxidant Damage Control

ENZYMATIC ANTIOXIDANTS

NON-ENZYMATIC ANTIOXIDANTS