Health = Oxidant / Antioxidant Balance - Meet Mr. ROS Hyde
Mr ROS Hyde
UNCONTROLLED ROS play a
role in Disease and Degenerative conditions
ROS Radical Attack!
UNCONTROLLED ROS can inflict damage
leading to health problems
Health Problems Resulting from Radical Damage
In trying to gain stability, by “stealing” (or donating)
an electron, ROS radicals quickly react with most nearby molecules,
including proteins, lipids, carbohydrates and DNA -
"attacked" molecule loses (or gains) an electron, it becomes a radical itself,
beginning a chain reaction which can result in the disruption of a living cell.
Most radicals can pull an electron from (i.e. oxidize)
most biochemical compounds -
The amount of
damage incurred is
dependent upon both the
number of radical hits, and the amount of protection by the antioxidant “damage
Each cell in the body is hit by
approximately 10,000 radicals every
ROS can inflict damage ("Oxidative Stress”)
to health problems
Its all about balance -
While oxygen and its
offspring are an essential part
of many, normal body processes,
aerobic cells may
damage if their
mechanisms are overwhelmed by excessive
E.g. The process of neutralizing
contained in unsaturated
oils use up the body’s
Examples of where ROS
are OVER-produced and
can result in significant damage to cells -
WBCs - neutrophils specialize in
ROS production, using them to kill invading pathogens.
Cells exposed to abnormal
environments - E.g.
Many drugs -
have oxidizing effects on cells
and lead to ROS
Ionizing radiation – is well known to generate
ROS within biological systems. Damage is higher in well oxygenated
tissues than in oxygen-deficient tissues.
Body components damaged by
can cause damage to the most
oxidatively-sensitive cellular components:
and nucleic acids (i.e. DNA, RNA).
This can cause local injury, cellular malfunction, and eventual organ
malfunction leading to a variety of diseases, or even death.
Damage to Unsaturated Lipids in Cell membranes and Lipoproteins -
Polyunsaturated fatty acids (PUFAs)
membranes and lipoproteins
are the key to bringing robust oxidation back to a
low-energy producing or fermenting cell.
However, unsaturated fatty acids will readily give
up an electron when attacked by ROS
in a self-perpetuating process called lipid peroxidation. The
breakdown of the resultant lipid hydroperoxides often involves transition
metal ion catalysis.
Cellular membranes and lipoproteins (vehicles
in which lipids travel in the bloodstream) are prominent targets of
undergoing numerous structurally and
functionally disruptive effects:
Increased membrane rigidity
Decreased activity of
membrane-bound enzymes - e.g. Sodium/Potassium pumps
Altered activity of
membrane receptors and altered electrolyte transport -
especially to sodium and calcium ions. Increased
intracellular sodium ion causes water to follow them causing cellular swelling.
Increased calcium ions damage mitochondria and cause “cellular hardening”, seen
in arterial plaque.
this rigidity is a common feature of aging.
mediate cellular injury
initiate peroxidation in the cellular, mitochondrial, nuclear, and
endoplasmic reticulum membranes - This increases the cellular
permeability for Ca2+ ions whose increased cellular
concentrations damage the mitochondria.
oxidize and degrade amino acids, and their oxidation of nuclear and
mitochondrial DNA, results in strand breaks and other types of DNA
Protein damage -
Proteins and nucleic acids have less reaction sites than PUFAs for
ROS reactions to propagate chain
reactions. Damage occurs only if radicals accumulate (which is not likely in
normal cells), or if the damage is focussed on a particular site of the protein,
such as if a protein binds a transition metal ion. [Marx G, Chevion M; 1986 and
Stadtman ER, Oliver CN; 1991].
Protein hydroperoxide -
Macquarie University, discovered a new form of free radical
damage to the body's proteins, called "protein hydroperoxide". They have since
gone on to show this same type of damage also occurs on the body’s cholesterol
carrying particles (lipoproteins).
DNA damage - Oxidising radicals readily attack
DNA if they are formed in its vicinity as seen in radiation. As with proteins
there seems little possibility that the damage may spread into a chain reaction.
Again for damage to occur it must either be site specific (leading to strand
breaks) or it must elude the repair systems before replication occurs leading to
Cheesman and Slater, 1993
The extreme reactivity and multiple intermediates of
oxygen make it difficult to detect and trace its course. Consequently, we
look for the "footprints" of oxygen reactions to determine cause-effect
relationships in stress responses.
Health Problems Resulting from Radical Damage
oxidative damages may be precursors to aging and diseases such as
cancer, heart disease,
mellitus, atherosclerosis, rheumatoid arthritis,
hypertension, sleep apnea, brain damage and dementia-related diseases such as
Alzheimer’s disease and Parkinson’s disease.
(or their metabolites)
are highly chemically
reactive and able to damage cells
(occurring even in healthy cells):
Attack cell membranes -
membrane dysfunction, altered receptor function;
Attack red blood
Deactivate enzymes, damage protein receptors;
Cause damage in DNA / RNA
which can trigger mutations in tissue and organs leading to cancer:
“Vegetable oils which are rich in linoleic
acid (eg. Corn and sunflower oils) are
potent promoters of tumor growth.”
Prof. R. Kearney, Sydney University, 1987;
cancer rates among women in China are associated with lipid peroxidized oils in
with polyunsaturated vegetable oils in a wok.
Cause damage in arteries /
atherosclerosis / heart disease -
resulting in plaque buildup. Endothelial cells, smooth muscle cell and
macrophages can release radicals, which cause lipid peroxidation. A continued
high level of unopposed oxidized lipids causes endothelial cell damage in blood
vessel walls and can lead to generation of foam cells and plaque, particularly
by oxidizing LDL, which can directly damage endothelial cells;
Cause damage in the skin -
wrinkles and premature aging;
Cause brain damage –
can lead to dementia;