Free radicals are highly reactive molecules that are produced through normal cell metabolism and environmental exposures. They can damage cells by reacting with lipids, proteins, and DNA if produced in excess. The body has antioxidant defenses like enzymes and nutrients that neutralize free radicals. However, oxidative stress occurs when there is an imbalance between free radical production and antioxidant defenses, leading to chronic diseases. While free radicals play beneficial roles in small amounts for immune function, too many can contribute to conditions like cancer, cardiovascular disease, neurological disorders, and more.

2. introduction
 A free radical is defined as any chemical species that contains
unpaired electrons, because of these free radicals are highly
reactive and readily take part in chemical reactions leading to tissue
injury
 They are produced either from normal cell metabolisms in situ or
from external sources (pollution, cigarette smoke, radiation,
medication).
 When an overload of free radicals cannot gradually be destroyed,
their accumulation in the body generates a phenomenon called
oxidative stress. This process plays a major part in the development
of chronic and degenerative illness such as cancer etc
 Endogenous and exogenous antioxidants act as “free radical
scavengers” by preventing and repairing damages caused by ROS
and RNS and enhance immune defence
pham-Huy.LA & et.al,free radical,antioxidants in disease and health,int j biomed sci ,2008 jun,v.4(2) :p 89-96

3. Free radical-targets
Free radicals attack three main cellular components.
Lipids:-
 Peroxidation of lipids in cell membranes can damage cell membranes by disrupting
fluidity and permeability.
 Lipid peroxidation can also adversely affect the function of membrane bound
proteins such as enzymes and receptors.
Proteins:-
 Direct damage to proteins can be caused by free radicals. This can affect many
kinds of protein, interfering with enzyme activity and the function of structural
proteins.
DNA:-
 Fragmentation of DNA caused by free radical attack causes activation of the poly
(ADP-ribose) synthetase enzyme, splits NAD+ to aid the repair of DNA.
 if the damage is extensive, NAD+ levels may become depleted to the extent that
the cell may no longer be able to function and dies.
 When a cell membrane or an organelle membrane is damaged by free radicals, it
loses its protective properties. This puts the health of the entire cell at risk.
Abheri Das Sarma et. al. Free Radicals and Their Role in Different Clinical Conditions ,International Journal of Pharma
Sciences and Research (IJPSR),Vol.1(3), 2010, 185-192

4. Formation of free radicals
• Normally, bonds don’t split to leave a molecule with an odd, unpaired
electron. But when weak bonds split, free radicals are formed.
• Free radicals are very unstable and react quickly with other compounds,
trying to capture the needed electron to gain stability. When the
"attacked" molecule loses its electron, it becomes a free radical itself,
beginning a chain reaction , resulting in the disruption of a living cell.
• Some free radicals may arise normally during metabolism and by immune
system’s cells purposefully to neutralize viruses and bacteria.

5. Steps involving free radical generation
 free radicals take part in radical addition and radical substitution
as reactive intermediates. Chain reactions involving free radicals
can usually be divided into three distinct processes: initiation,
propagation, and termination.
 Initiation reactions are those, which result in a net increase in the
number of free radicals. They may involve the formation of free
radicals from stable species or they may involve reactions of free
radicals with stable species to form more free radicals.
 Propagation reactions involve free radicals in which the total
number of free radicals remains the same.
 Termination reactions are those reactions resulting in a net
decrease in the number of free radicals.
 Radicals may also be formed by single electron oxidation or
reduction of an atom or molecule. An example is the production of
superoxide by the electron transport chain.
Abheri Das Sarma et. al. Free Radicals and Their Role in Different Clinical Conditions ,International Journal of Pharma Sciences and
Research (IJPSR),Vol.1(3), 2010, 185-192

6. CAUSES OF FREE RADICALS
 Pollution and other external substances:- The pollutants produced by modern
technologies often generate free radicals in the body. The food most of us buy
contains farm chemicals, including fertilizers and pesticides, that produce free
radicals when we ingest them.
 Prescription drugs often have the same effect, their harmful side-effects may be
caused by the free radicals they generate.
 Processed foods frequently contain high levels of lipid peroxides, which produce
free radicals that damage the cardiovascular system.
 Cigarette smoke generates high free-radical concentrations , much of the lung
damage associated with smoking is caused by free radicals.
 Air pollution , Alcohol is a potent generator of free radicals
 Stress:- The body's stress response creating free radicals in abundance.
 The stress response races the body's energy-creating apparatus, increasing the
number of free radicals as a toxic by-product
 The hormones that mediate the stress reaction in the body - cortisol and
catecholamines - will themselves degenerate into particularly destructive free
radicals

7. CAUSES OF FREE RADICALS
Production of free radicals in the body is continuous and inescapable
The basic causes include the following:
The immune system:-
 The body tries to harness the destructive power of the most dangerous
free radicals - the oxy radicals and ROS - for use in the immune system and
in inflammatory reactions.
 Certain cells in these systems engulf bacteria or viruses, take up oxygen
molecules from the bloodstream, remove an electron to create a flood of
oxy radicals and ROS, and bombard the invader with the resulting toxic
shower.
 This aggressive use of toxic oxygen species is remarkably effective in
protecting the body against infectious organisms.
Energy production:-
 The energy-producing process in every cell generates oxy radicals and ROS
as toxic waste, continuously and abundantly
 Oxygen is used to burn glucose molecules that act as the body's fuel.
 The cell includes a number of metabolic processes with the constant
creation of oxy radicals and ROS.
Abheri Das Sarma et. al. Free Radicals and Their Role in Different Clinical Conditions ,International Journal of Pharma
Sciences and Research (IJPSR),Vol.1(3), 2010, 185-192

8. FREE RADICAL DEFENSES
 Given the many sources of free radicals, it is not surprising
that all aerobic forms of life maintain and elaborate anti-free-
radical defense systems, also known as antioxidant systems.
 Enzymes:-Every cell in the body creates its own "bomb
squad"-antioxidant enzymes whose specialty is defusing oxy
radicals and ROS. superoxide dismutase (SOD), takes hold of
molecules of superoxide - a particularly destructive free
radical and changes them to a much less reactive form.
 SOD and another important antioxidant enzyme set, the
glutathione system, work within the cell.
 Nutrients:-second line of defense
 body makes use of many standard vitamins and other
nutrients to quench the oxy radicals' thirst for electrons
 Among the many substances used are Vitamins C and E, beta-
carotene, and bioflavonoids.
Abheri Das Sarma et. al. Free Radicals and Their Role in Different Clinical Conditions ,International Journal of Pharma
Sciences and Research (IJPSR),Vol.1(3), 2010, 185-192

9. FREE RADICAL DEFENSES
 Self repair:-The body also has systems to repair or replace
damaged building blocks of cells.
 For example, the system for repairing damage to DNA and
other nucleic acids is particularly elaborate and efficient, with
various specialized enzymes that locate damaged areas, snip
out ruined bits, replace them with the correct sequence of
molecules, and seal up the strand once again.
 Most protein constituents in the cell, for example, are
completely replaced every few days. Scavenger enzymes
break used and damaged proteins into their component parts
for reuse by the cell.
Abheri Das Sarma et. al. Free Radicals and Their Role in Different Clinical Conditions ,International Journal of
Pharma Sciences and Research (IJPSR),Vol.1(3), 2010, 185-192

10. Role of free radicals in pathogenesis
 When produced in excess, free radicals and oxidants generate a
phenomenon called oxidative stress, a deleterious process that can
seriously alter the cell membranes and other structures such as
proteins, lipids, lipoproteins, and deoxyribonucleic acid (DNA)
 oxidative stress results from an imbalance between formation and
neutralization of ROS/RNS
 Cancer and oxidative stress:-
 oxidative DNA damage is responsible for cancer development.
 Cancer initiation and promotion are associated with chromosomal
defects and oncogene activation induced by free radicals
 Oxidative DNA damage also produces a multiplicity of modifications
in the DNA structure including base and sugar lesions, strand breaks
DNA-protein cross-links and base-free sites
 For example, tobacco smoking and chronic inflammation resulting
from noninfectious diseases like asbestos are sources of oxidative
DNA damage that can contribute to the development of lung cancer
and other tumors
pham-Huy.LA & et.al, free radical, antioxidants in disease and health ,int j biomed sci ,2008 jun,v.4(2) :p 89-96

11. Cardiovascular disease and oxidative stress
 Oxygen free radicals are highly reactive compounds causing peroxidation of
lipids and proteins and are thought to play an important role in the
pathogenesis of reperfusion abnormalities including myocardial stunning,
irreversible injury, and reperfusion arrhythmias.
 Potential sources of free radicals during ischemia and reperfusion have been
identified in myocytes, vascular endothelium, and leukocytes.
 Injury to processes involved in regulation of the intracellular Ca2+ concentration
may be a common mechanism underlying both free radical- induced and
reperfusion abnormalities.
Kidney
 Mitochondrial free radical production induces lipid peroxidation during
myohemoglobinuria.
 Iron catalyzed free radical formation and lipid peroxidation are accepted
mechanisms of heme protein-induced acute renal failure.
 In conclusion, the terminal mitochondrial respiratory chain is the dominant
source of free radical.
Abheri Das Sarma et. al. Free Radicals and Their Role in Different Clinical Conditions ,International Journal of Pharma
Sciences and Research (IJPSR),Vol.1(3), 2010, 185-192

12. Neurological disease and oxidative stress
 Oxidative stress has been investigated in neurological diseases including
Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, memory
loss, depression.
 In Alzheimer’s, numerous experimental and clinical studies have
demonstrated that oxidative damage plays a key role in the loss of
neurons and the progression to dementia .
 The production of ß-amyloid, a toxic peptide often found present in
Alzheimer’s patients’ brain, is due to oxidative stress and plays an
important role in the neurodegenerative processes
Rheumatoid arthritis and oxidative stress
 Rheumatoid arthritis is an autoimmune disease characterized by chronic
inflammation of the joints and tissue around the joints with infiltration
of macrophages and activated T cells
 The pathogenesis of this disease is due to the generation of ROS and
RNS at the site of inflammation.
 Oxidative damage and inflammation in various rheumatic diseases were
proved by increased levels of isoprostanes and prostaglandins in serum
and synovial fluid compared to controls
pham-Huy.LA & et.al , free radical, antioxidants in disease and health , int j biomed sci , 2008 jun,v.4(2) :p 89-96

13. Nephropathy and oxidative stress
 Oxidative stress plays a role in a variety of renal diseases such as
glomerulonephritis and tubulointerstitial nephritis, chronic renal
failure, proteinuria, uremia .
 The nephrotoxicity of certain drugs such as cyclosporine, tacrolimus ,
gentamycin, bleomycin, vinblastine, is mainly due to oxidative stress
via lipid peroxidation .
 Heavy metals and transition metals act as free radical inducers
causing different forms of nephropathy and carcinogenicity
Ocular disease and oxidative stress
 Oxidative stress is implicated in age-related mascular degeneration
and cataracts by altering various cell types in the eye either
photochemically or nonphotochemically .
 Under the action of free radicals, the crystalline proteins in the lens
can cross-link and aggregate, leading to the formation of cataracts .
 In the retina, long-term exposure to radiation can inhibit mitosis in
the retinal pigment epithelium and choroids, damage the
photoreceptor outer segments, and has been associated with lipid
peroxidation
pham-Huy.LA & et.al, free radical, antioxidants in disease and health ,int j biomed sci ,2008 jun,v.4(2) :p 89-96

14. Free radicals in beneficial role
 Free radicals perform many critical functions in our bodies in
controlling the flow of blood through our arteries, to fight
infection, to keep our brain alert and in focus.
 Phagocytic cells involved in body defense produce and
mobilize oxygen free radicals to destroy the bacteria and
other cells of foreign matter which they ingest.
 Similar to antioxidants, some free radicals at low levels are
signaling molecules, i.e. they are responsible for turning on
and off of genes.
 Some free radicals such as nitric oxide and superoxide are
produced in very high amount by immune cells to poison
viruses and bacteria.
 Some free radicals kill cancer cells , In fact certain cancer
drugs aim in increasing the free radical amount in body.
Abheri Das Sarma et. al. Free Radicals and Their Role in Different Clinical Conditions ,International Journal of Pharma
Sciences and Research (IJPSR),Vol.1(3), 2010, 185-192