Free radicals reactive oxygen species and reactive nitrogen species are generated by our body by various endogenous systems, exposure to different physiochemical conditions or pathological states. A balance between free radicals and antioxidants is necessary for proper physiological function. If free radicals overwhelm the body's ability to regulate them, a condition known as oxidative stress ensues. Free radicals thus adversely alter lipids, proteins, and DNA and trigger a number of human diseases. Free radicals are a main cause of cardiovascular diseases, cancer, aging and immune defense disorders. Foods like berries and carrot protect us against free radicals.
2. • Free radicals are highly reactive substances produced
continuously during metabolic processes.
• They participate mainly in physiological events such as
the immune response, metabolism of unsaturated fatty
acids, and inflammatory reaction.
• The balance between free radicals and antioxidants is
disrupted in many diseases.
Introduction
3. Introduction
This disruption may be attributed to a number
of factors .
the inability of the cells
to produce sufficient
amounts of antioxidants
the excess production
of reactive oxygen
species
4. • Free radical excess results in impairment of
1. DNA
2. enzymes
3. Membranes
Induces changes in the activity of the immune
system .and in the structure of basic
biopolymersWhich is related to mutagenesis and
aging processes.
Introduction
5. • The free radical can be defined as a chemical
species, an atom or molecule that has one or more
unpaired electrons in valance shell.
• As free radical contains an odd number of electron,
which .make it unstable.
• it can react quickly with other compound, trying to
capture the needed electron to gain stability.
FREE RADICAL CHEMISTRY
6. • Generally, free radical attacks the nearest stable molecule"
stealing" its electron. When the attacked molecule loses its
electron, it becomes a free radical itself, beginning a chain
reaction cascade resulting in disruption of a living cell.
FREE RADICAL CHEMISTRY
7. • A) Covalent bond cleavage of normal molecule or
atom: Atoms are blinded together when they share or
transfer electron to form molecule. A covalent bond is
formed when a pair of electron is shared.
HOW FREE RADICALS ARE FORMED ?
8. • The bond breakage occurs in two ways “hemolytic
cleavage” in this type of cleavage both atoms retain
one electron each due to symmetrical rupture of
bond.
H-H →H° + H°
• Such type of cleavage requires high energy input
either in the form of high temperature, U.V light or
ionizing radiation to cause hemolysis of covalent
bond.
HOW FREE RADICALS ARE FORMED ?
9. B) Electron transfer: Electron transfer is a far more
common an important source of generation of free
radicals in biological system.
i) Oxidation reaction: By loss of a single electron from a
normal molecule.
ii) Reduction reaction: By addition of a single electron to
a normal molecule
H-H→ H¯ + H+
HOW FREE RADICALS ARE FORMED ?
10. • The most important free radicals in biological system
are radical derivatives of oxygen.
• (reactive oxygen species )ROS includes free radical as
well as other non-radical derivatives of oxygen e.g. H
O & Singlet Oxygen. These ROS can produce
oxidative damage to the tissue and hence are known
as oxidants in biological system.
SOURCES OF FREE RADICAL
11. There are two important sources of reactive oxygen species
:generation in the biological system
SOURCES OF FREE RADICAL
12.
13. • Reactive oxygen species, in particular OH•, can react
with all biological macromolecules (lipids, proteins,
nucleic acids, and carbohydrates). The initial reaction
generates a second radical, which can react with a
second macromolecule to continue the chain reaction.
Mechanism of action
14. • Proteins are modified in structure and function by radical
reactions. Metal-catalyzed protein oxidation results in
addition of carbonyl groups or cross-linking or
fragmentation of proteins.
• Lipid (peroxidation) aldehydes can react with sulfhydryl
(cysteine) or basic amino acids (histidine, lysine).
Similarly, modification of individual nucleotide bases,
single-strand breaks and cross-linking are the typical
effects of reactive oxygen species on nucleic acids.
Mechanism of action
15. • The immune system uses the lethal effects of oxidants by
making production of oxidizing species a central part of its
mechanism of killing pathogens; with activated phagocytes
producing both ROS and reactive nitrogen species.
DISEASES
Immune defense
16. • These include superoxide (•O−2), nitric oxide (•NO) and their
particularly reactive product, peroxynitrite (ONOO-).
• Although the use of these highly reactive compounds in the
cytotoxic response of phagocytes causes damage to host
tissues, the non-specificity of these oxidants is an advantage
since they will damage almost every part of their target cell
Immune defense
17. • Reactive oxygen and nitrogen species, such as super oxide
anion, hydrogen peroxide, hydroxyl radical, and nitric oxide
and their biological metabolites also play an important role in
carcinogenesis.
• ROS induce DNA damage, as the reaction of free radicals with
DNA includes strand break base modification and DNA protein
cross-links.
Role of oxygen free radicals in cancer development
18. • Endothelium is the bioactive inner layer of the blood
vessels, which serves as an important locus on control of
vascular and thus other organ functions regulating
vascular tone permeability. It produces components of
extracellular matrix such as collagen and a variety of
regulatory mediators, including NO.
• Endothelial dysfunction (ED) is an early event in
atherosclerotic disease.
Free radicals in cardiovascular diseases
19. • . The theory proposes that aging is actually caused by the
toxicity of ROS through a vicious cycle in which ROS
damage to the constituents of mitochondria leads to the
generation of more ROS .
• there is a strong correlation between chronological age
and the level of ROS generation and oxidative damage.
• mitochondrial function is gradually lost during aging.
Free-radical theory of aging
20. • Aging is also associated with an increase in the levels of
oxidatively damaged proteins, lipids and DNA .
• Aging in mammals is universal, degenerative, and
appears unavoidable even in very sheltered
environments.
Free-radical theory of aging
22. Antioxidant
• Antioxidant is a molecule that inhibits the
oxidation of other molecules.
• Oxidation reactions can produce free radicals. In
turn, these radicals can start chain reactions.
When the chain reaction occurs in a cell, it can
cause damage or death to the cell.
• Antioxidants terminate these chain reactions by
removing free radical intermediates, and inhibit
other oxidation reactions.
• The lichens have played an important role as a
source for new antioxidant agents.
23. Antioxidant
• Antioxidants are classified into two broad
divisions, depending on whether they are soluble In
water (hydrophilic) or in lipids (lipophilic).
• These compounds may be synthesized in the body
or obtained from the diet.
antioxidants react
with oxidants in the
cell cytosol and the
blood plasma
antioxidants protect
cell membranes
from lipid
peroxidation.
24. Antioxidant metabolite Solubility
Concentration in
human serum
(μM)
Concentration in
liver tissue
(μmol/kg)
Ascorbic acid (vitamin
C)
Water 50 – 60 260 (human)
Glutathione Water 4 6,400 (human)
Lipoic acid Water 0.1 – 0.7 4 – 5 (rat)
Uric acid Water 200 – 400 1,600 (human)
Carotenes Lipid
β-carotene: 0.5 –
1
retinol (vitamin
A): 1 – 3
5 (human, total
carotenoids)
α-Tocopherol (vitamin
E)
Lipid 10 – 40 50 (human)
Ubiquinol (coenzyme Q) Lipid 5 200 (human)
25. • They do this by being oxidized themselves, so
antioxidants are often reducing agents.
26. • an imbalance between the production of reactive
species and antioxidant defense activity, and its
enhanced state has been associated with many of the
chronic diseases such as: cancer, diabetes,
neurodegenerative and cardiovascular diseases .
Oxidative stress
27. • many research groups have driven efforts to
assess the antioxidant properties of natural
products.
• These properties have been investigated through
either chemical (in vitro) or biological (in vivo)
methods, or both .
• these researches have led some to suggest that the
long-term consumption of food rich in
antioxidants can retard or avoid the occurrence of
such diseases .
Oxidative stress
28. • There are two techniques:
1. First, it maximizes antioxidant intake from foods and
supplements.
2. second, it minimizes factors that promote the formation of
free radicals.
• here are the basics:
1. Choose organic,additive-free foods.
2. Drink only purified water.
3. Avoid exposure to volatile chemicals.
4. Limit exposure to air pollution
Protect ourselves from free radical and long our life
29. 5. limit the amount of time you spend in direct sunlight.
6. Check your house for radon gas.
7. Get medical and dental x-rays only when absolutely necessary.
8. Take medications only when absolutely necessary.
• people with low intakes of antioxidant-rich fruits and vegetables
were at greater risk for developing these chronic conditions than
were people who ate plenty of these fruits and vegetables.
Protect ourselves from free radical and long our life
30. • Foods rich in antioxidants :
1. Berries: blueberries, cranberries and blackberries.
2. Carrots: Fresh, crisp carrots beta carotene.
3. Green Vegetables: Vegetables of all colors .
4. Grains: the immunity-boosting compounds.
5. Legumes: vitamin E
6. Green Tea: neutralize harmful free radicals.
Protect ourselves from free radical and long our life