Free radicals are unstable, highly reactive molecules which are generated both in the body and outside the body. They are described as electron hungry molecules produced when oxygen is metabolized or burned by the body Role of Free Radical in diseases

1. GENERATION OF FREE RADICAL AND ITS
ROLE IN DISEASES

2. INTRODUCTION
• Free radicals are unstable, highly reactive molecules
which are generated both in the body and outside the
body. They are described as electron hungry molecules
produced when oxygen is metabolized or burned by the
body.
• They travel via cells disrupting the structure of
molecules causing cellular damage. They do serve useful
purposes in the human body and under certain
situations have several deleterious effects in the body.
The changes induced by free radicals are believed to be
a major cause of aging, disease development and death.

3. GENERATION OF FREE RADICALS
By either of mechanisms:
 First, from the normal metabolism of oxygen requiring
nutrients: Mitochondria-the intracellular powerhouse
which produces the universal energy molecules
Adenosine triphosphate (ATP) normally consume
oxygen in the process and convert it to water. However
unwanted by-products such as hydrogen peroxide and
hydroxyl radical are inevitably produced due to
incomplete reduction of the oxygen molecule. It has
been estimated that more than 20 billion molecules of
oxidants are produced per day by each cell during
normal metabolism.

5.  Secondly, white blood cells destroy parasites, bacteria and viruses by using
oxidants (free radicals) such as nitric oxide, super oxide and hydrogen
peroxide. This is done by the release of free radicals to destroy invading
pathogenic microbes as part of the body’s defense mechanism against
diseases but with electrons unhinged, free radicals roam the body
wrecking havoc. The free radical in an effort to achieve stability attacks
nearby molecules in order to obtain another electron, and once this is
done the attacked molecules become damaged. When the attacked
molecule losses its electron, it becomes a free radical itself, beginning a
chain reaction. Once the process is started it can cascade finally resulting
in the disruption of living cells, which in turn rip through the tissues and
ultimately results in tissue damage.

6.  Thirdly other cellular components called peroxisomes
produce hydrogen peroxide as a by-product of the
degradation of fatty acids and other molecules. In contrast
to the mitochondria which oxidizes fatty acids to produce
ATP and water, peroxisomes oxidizes fatty acids to produce
heat and hydrogen peroxide. The peroxide is then
degraded by an enzymatic antioxidant called catalase.
Under certain conditions some of the hydrogen peroxide
escapes to wreak havoc in other compartments in the cell.
Polyunsaturated fats contribute immensely to the over
production of free radicals because they have multiple
double bonds which become oxidized and cause an
increased production of free radicals in the form of lipid
peroxide radicals.

8.  Finally an enzyme in the cells called cytochrome P450 is
one of the body’s primary defenses against toxic chemicals
ingested with food. The induction of these enzymes to
prevent damage by toxic foreign chemicals like drugs and
pesticides also result in the production of oxidant by-
products. Virtually all organs and tissues in the body are
under constant attack by these free radicals behaving like
biological terrorists ripping through our bodies and they
need to be stopped quickly. To prevent free radical
damage, the body has a defense system called
antioxidants. Antioxidants are molecules which can safely
interact with free radicals and terminate the chain
reactions before vital molecules are damaged.

10. Role of Free Radical in diseases
 Free radical reactions are expected to produce progressive
adverse changes that accumulate with age throughout the
body. Fortunately the body is naturally equipped with
antioxidants defense system to detoxify these dangerous
agents but unfortunately the body’s defense system
becomes less effective as we get older leading to
accumulation of oxidative damage and the development of
chronic degenerative diseases.
 Irrespective of how and why free radicals are produced,
they are harmful and can impair vital molecules within the
body such as lipids, protein and DNA. These result to
oxidative stress. It also affect cellular calcium metabolism if
uncontrolled, and this can result in cell injury or death.

11.  Oxidative stress causes damage to three major structures: DNA,
Lipids and Proteins. The damage to DNA strands can occur directly
by free radical in close proximity to the DNA or indirectly, by
impairing production of protein needed to repair DNA. Alteration
in DNA is a major factor in the development of cancer. The
oxidative damage to DNA overtime could cause changes to both
the structure and functions of chromosomes, which can lead to
cancer and chronic diseases.
 Free radical could attack fatty acid side chains of intracellular
membranes and lipoproteins. A chain reaction known as lipid
peroxidation . The product of lipid peroxidation can further
damage membrane proteins making the cell membrane ‘leaky’
and eventually leading to loss of membrane integrity. Lipid
peroxidation is implicated in the development of arteriosclerosis.

12.  The last structures damaged by oxidative stress are cellular
proteins. This plays a role in the causation of cataracts. Free
radicals can interfere with protein function leading to irregular,
abnormal metabolism and rapid aging . Oxidative stress (free
radical reactions) occurs in most human diseases. This is not to say
that oxidative stress is the cause of most diseases. The increase in
free radicals may be secondary to the disease process.
 Clinical conditions associated with free radical damage include the
following diseases stated below: Alzheimer, Diabetes, Amyotropic
lateral sclerosis, Coronary artery diseases, Arthritis, Heart failure,
Arteriosclerosis, Hypertension and many other diseases. In fact
free radicals are believed to play a role in more than 60 different
health conditions.

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