ANTIOXIDANT / OXIDANT BALANCE:
Antioxidant /
Oxidant Balance:
Where do reactive oxygen species (ROS) come from in body?
Where do Body's ROS
Come From?
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
(1) ROS are produced
in the body in day-to-day life
ROS produced by metabolism (energy synthesis)
/ RespirationROS 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).
ROS are leaked from the Electron Transport Chain (ETC).
superoxide radicals generated 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 •- )
- 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
ROS Produced
by Red Blood CellsRed blood cells produce
ROS during
the binding and release of oxygen
and carbon dioxide
by hemoglobin.
ROS Produced
by WHITE Blood CellsThe 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 radicals,
ROS, RNS or other reactive oxidants are released by immune system white blood cells (E.g. macrophages).
Emotional stress
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
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
• -
) ,
H2 O2 & 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. 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
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 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
H2 O2 .
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
to accelerate the rate of damage.
ROS produced
by hyperglycemiaHyperglycemia
(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
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
ROS Produced by OTHER BODY
PROCESSESROS 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 diabetes.
ROS
can be directly introduced into the bodyROS in oxidized
/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 fats
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.Dietaryomega-3 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
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). Nutritionist/author Dr. Mary Enig maintains that saturated
fats actually LOWER Lp(a) levels.
- Decrease
HDL.
Damaged/Altered/Toxic Fats
Healing Therapies
Ozone therapy, hydrogen peroxide therapy
and PDT. Deliberately introduce controlled amounts ROS
into the body.
References J Lipid Res 1992 Oct;33(10):1493-501
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
• -
) .
H2 O2
O2
•
-
OH•
and
HOCl
by bacteria
Rosen H, Rikata R, Waltersdorph
AM, Klebanoff S; 1987
H2 O2
O2
•
-
are not reactive enough to destroy microbes
themselves, and must be converted to
OH•,
1 O2 *
,
HOCl
or other oxidizing agent. However, the slow reactivity
of H2 O2
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
1 O2 *
