Free Radical:A free radical is an atom capable of independent existence (hence the term “free”) that

contains one or more unpaired electrons in its outer orbital.It is an electron-deficient species.It is
represented by a superscript dot to the right.(R●)

6 Important characteristics
Free radicals are:Highly reactive.Unstable and try to become stable.Short life span ( Short-lived ) as
they tend to catch an electron from other molecules.

7 Types of Free Radicals Oxygen free radicals (OFR)

Nitrogen free radicals (NFR)Lipid free radicals (LFR)Others: chlorine radicals(Cl ●) ,carbon
radicals(CCl3●), sulfur radicals (RS ● ).

8 Oxygen free radicals (OFR)

OFR is referred to oxygen-derived free radicals.The unpaired electron is located on O such as
superoxideradical and hydroxyl radical▲ Reactive oxygen species (ROS)ROS is a collective term
that includes both oxygen free radicals (OFR), and non radicals that are oxidizing agents and / or are
easily converted into radicals such as hydrogen peroxide and singlet oxygen.H2O2、 1O2Non free
radical ROSFree radical ROSROSOFR（O2、OH•）.

9 Nitrogen free radicals (NFR)

NFR is defined as nitrogen-derived free radicals. RNS:NO•ONOO , NO2RNSLipid free radicals
(LFR)Lipid free radicals are referred to middle metabolic products resulting from the chain reaction of
lipid peroxidation, which is produced by interaction of OFR and unsaturated fatty
acid.L•LO•LOO•LFR

10 Sources of Free Radicals

Exogenous sources of free radicals:Ionizing radiationUltraviolet radiationChemicals,
smokingPollutionDiet(fatty and processed foods)Endogenous sources of free
radicals:RespirationMetabolism.InflammationPhagocytosis

12 Roles of Free Radicals in Biological Systems

Like two-edged sword:It can be beneficial.It can be harmful.They play an important role in a number
of biological processes, many of which are necessary for life.But they also cause damage and
disease.

13 Free Radicals: Positive Effects

The presence of low concentrations of free radicals is important for normal cellular redox status and
immune function.Immune system: Free radicals are used by phagocytic cells to kill bacteria during
infections. (Antimicrobial actions).Modify oxidation-reduction (redox) states.Nitric oxide (NO●) helps
to regulate blood pressure .However, there is now clear evidence that ROS are not merely toxic
species but also—within certain concentrations—useful signaling molecules regulating physiological
processes.Nitric oxide (NO) derivatives and reactive oxygen species (ROS) modulate contractile
function of respiratory and limb skeletal muscleDuring intense skeletal muscle contractile activity
myotubes' mitochondria generate high ROS flows: this renders skeletal muscle a tissue where ROS
hold a particular relevance

14 Free Radicals: Negative Effects

Damage produced by FRsFree radicals attack the nearest stable molecule, "stealing" its
electron.When the "attacked" molecule loses 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 a
living cell.Almost all biological macromolecules are damaged by the free radicals

15 They attack sites of increased electron density such as:

The nitrogen atom present in proteins and DNA predominantlyCarbon-carbon double bonds present
in polyunsaturated fatty acids and phospholipidsto produce additional free radical, often reactive,
intermediates.However, excessive production can provoke inflammation or altered cellular functions
through:lipid peroxidationprotein modificationDNA modification (DNA is damaged by strand
breaks)The DNA damage may directly cause inhibition of protein and enzyme synthesis and
indirectly cause cell death or mutation and carcinogenesisWhich compromises cell function leading
to cell death.

16 Mechanism of radical reactions

Radicals are highly reactive speciesThree distinct stepsInitiation (homolytic covalent bonds
cleavage)Propagation (chain propagation)Termination

17 Oxidative damage to lipids - Lipid peroxidation

Peroxidation (auto-oxidation) of lipids exposed to oxygen is responsible not only for deterioration of
foods (rancidity) but also for damage to tissues in vivo, where it may be a cause of cancer,
inflammatory diseases, atherosclerosis, and aging.The deleterious effects are considered to be
caused by free radicals (ROO•, RO•, OH•) produced during peroxide formation from fatty acids
containing methylene-interrupted double bonds, ie, those found in the naturally occurring
polyunsaturated fatty acids.Lipid peroxidation is a chain reaction providing a continuous supply of
free radicals that initiate further peroxidation.

18 lipid peroxidation Initiation RH + X• R• + XH 2. Propagation

R• + O ROO•ROO• + RH R• + ROOH , etc.3. TerminationROO• + ROO• ROOR + O2R• + ROO•
ROORR• + R• RR

19 Counteracting free radical damage

The human body has several mechanisms to counteract damage by free radicals and other reactive
oxygen species.One important line of defense against free radical damage is the presence of
antioxidants.Some such antioxidants, are produced during normal metabolism in the body.Other
lighter antioxidants are found in the diet.

20 AntioxidantsSubstances that are able to neutralize reactive molecules and reduce oxidative
damage.Result of metabolic processes and environmental sources.Certain antioxidant vitamins
donate their electrons or hydrogen molecules to free radicals to stabilize them.Antioxidant minerals
function within complex antioxidant enzyme systems that convert free radicals to less damageing
substances that are excreted by our bodies. These enzymes also break down fatty acids that have
become oxidized. In breaking down the fatty acids they destroy the free radicals associated with the
oxidized fatty acids.SOD – converts free radicals to hydrogen peroxidecatalase – removes hydrogen
peroxide from our bodies by converting it to water and hydrogenglutathione peroxidase – also
removes hydrogen peroxide and stops the production of free radicals in lipidsAntioxidants, vit E, C
possibly A, beta-carotene and seleniumCopper zinc and manganese are part of SOD.Iron cofactor
for catalase antioxidant enzymeEnvironmental - air pollution, cigarette smokeEither act as
antioxidant or are part of enxyme that does (Zn, Cu, Mn)

22 Pro-oxidant & Antioxidant Balance

Damage(Pro-oxidants)Damage(Pro-oxidants)Defense(Antioxidants)Defense(Antioxidants)Decrease
of antioxidant defense systemOxidative damage
23 Oxidative stress It is an excess of free-radicals damages cells.
Oxidative stress has been identified as a causative factor in:Cognitive performanceAging
processDevelopment of diseases such as cancer, arthritis, cataracts, and heart disease

24 Free Radical Diseases Stroke Alzheimer’s Parkinson’s

Photo-aging (wrinkles)Macular Degeneration& CataractsPeriodontitisEmphysemaLung
CancerCoronary Heart DiseaseDiabetesHypertension &Chronic Kidney DiseaseAlcohol &Viral Liver
DiseasesProstate CancerRheumatoid ArthritisColo-rectal CancerPeripheral Vascular DiseaseSkin
Cancer &MelanomaOsteoarthritis

25 Many of the changes associated with aging are actually due to the effects of free-radicals.
As we age, the antioxidant enzyme systems work less efficiently.

26 Antioxidant System in our body

The enzymatic antioxidants:Superoxide dismutase (SOD) eliminates the superoxide (O2-.).Catalase
and the glutathione peroxidase eliminate hydrogenperoxide (H2O2).The non enzymatic
antioxidants:Vitamins E, C, A or Pro vitamin A(beta-carotene).

27 Vitamin C Vitamin C, or ascorbic acid, is a water-soluble vitamin.

This vitamin is a free radical scavenger.It is effective in protecting tissues against oxidative
damage.Its protective effects extend to cancer, coronary artery disease, arthritis and aging.

28 Vitamin E Vitamin E is a fat-soluble substance

It is a principal antioxidant in the body and protects polyunsaturated fatty acids in cell membranes
from peroxidation.

29 2 types of Antioxidants (1) - Preventative antioxidants:

Reduce the rate of chain initiatione.g.: catalase and other peroxidases that react with ROOH and
chelators of metal ions such as EDTA(2) - Chain-breaking Antioxidants:Which interfere with chain
propagation.e.g.: In vivo, superoxide dismutase, which acts in the aqueous phase to trap superoxide
free radicals (O2 −•); perhaps urate ; and vitamin E, which acts in the lipid phase to trap ROO•
radicals.

30 What do antioxidants do?

Provides key nutrients needed by the body to neutralize free radicals.Aid the human body’s natural
defenses.Repair oxidative damage.Slow or prevent damage to body cells.May exhibit anti-aging
benefits.May improve immune function and lower risk for infection and cancer.

31 Table 1. Reactive Oxygen Species and Antioxidants that Reduce Them

Reactive SpeciesAntioxidantSinglet oxygen 1O2Vitamin A, vitamin ESuperoxide radical (O2-
)superoxide dismutase, vitamin CHydrogen peroxide (H2O2)Catalase; glutathione
peroxidasePeroxyl radical (ROO)Vitamin C, vitamin ELipid peroxyl radical (LOO)Vitamin
EHydroxyl radical (OH)Vitamin C

32 SummaryOne of the most significant sites of free radical damage is the cell membrane. May
affect all systems affected by this cell.Other sites of damage include LDL, cell proteins and our
genetic material (DNA). May increase our risk for heart disease and cancer and cause our cells to
die prematurely.
33 ConclusionAntioxidant plays an important role to prevent cancer, and other disease. They also
have role in slowing aging process and preventing heart disease. So antioxidant are very much
necessary for our body .But our body can’t manufacture these chemicals, so they must be supplied
through diet.