Presented by

Ahmed Alaa

Mohammed Shehata Sakr

Under supervision ofDr/ Noha El-khodary

• Free radicals are highly reactive substances producedcontinuously during metabolic processes.

• They participate mainly in physiological events such asthe immune response, metabolism of unsaturated fattyacids, and inflammatory reaction.

• The balance between free radicals and antioxidants isdisrupted in many diseases.

Introduction

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

• Free radical excess results in impairment of

1. DNA

2. enzymes

3. Membranes

Induces changes in the activity of the immunesystem .and in the structure of basicbiopolymersWhich is related to mutagenesis andaging processes.

Introduction

• The free radical can be defined as a chemicalspecies, an atom or molecule that has one or moreunpaired 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 tocapture the needed electron to gain stability.

FREE RADICAL CHEMISTRY

• Generally, free radical attacks the nearest stable molecule"stealing" its electron. When the attacked molecule loses itselectron, it becomes a free radical itself, beginning a chainreaction cascade resulting in disruption of a living cell.

FREE RADICAL CHEMISTRY

• A) Covalent bond cleavage of normal molecule oratom: Atoms are blinded together when they share ortransfer electron to form molecule. A covalent bond isformed when a pair of electron is shared.

HOW FREE RADICALS ARE FORMED ?

• The bond breakage occurs in two ways “hemolyticcleavage” in this type of cleavage both atoms retainone electron each due to symmetrical rupture ofbond.

H-H →H° + H°

• Such type of cleavage requires high energy inputeither in the form of high temperature, U.V light orionizing radiation to cause hemolysis of covalentbond.

HOW FREE RADICALS ARE FORMED ?

B) Electron transfer: Electron transfer is a far morecommon an important source of generation of freeradicals in biological system.i) Oxidation reaction: By loss of a single electron from anormal molecule.ii) Reduction reaction: By addition of a single electron toa normal molecule

H-H→ H¯ + H+

HOW FREE RADICALS ARE FORMED ?

• The most important free radicals in biological systemare radical derivatives of oxygen.

• (reactive oxygen species )ROS includes free radical aswell as other non-radical derivatives of oxygen e.g. HO & Singlet Oxygen. These ROS can produceoxidative damage to the tissue and hence are knownas oxidants in biological system.

SOURCES OF FREE RADICAL

There are two important sources of reactive oxygen species :generation in the biological system

SOURCES OF FREE RADICAL

• Reactive oxygen species, in particular OH•, can reactwith all biological macromolecules (lipids, proteins,nucleic acids, and carbohydrates). The initial reactiongenerates a second radical, which can react with asecond macromolecule to continue the chain reaction.

Mechanism of action

• Proteins are modified in structure and function by radicalreactions. Metal-catalyzed protein oxidation results inaddition of carbonyl groups or cross-linking orfragmentation 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 typicaleffects of reactive oxygen species on nucleic acids.

Mechanism of action

• 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

• These include superoxide (•O−2), nitric oxide (•NO) and their particularly reactive product, peroxynitrite (ONOO-).

• Although the use of these highly reactive compounds in thecytotoxic response of phagocytes causes damage to hosttissues, the non-specificity of these oxidants is an advantagesince they will damage almost every part of their target cell

Immune defense

• 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

• Endothelium is the bioactive inner layer of the bloodvessels, which serves as an important locus on control ofvascular and thus other organ functions regulatingvascular tone permeability. It produces components ofextracellular matrix such as collagen and a variety ofregulatory mediators, including NO.

• Endothelial dysfunction (ED) is an early event in atherosclerotic disease.

Free radicals in cardiovascular diseases

• . 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

• 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

Antioxidant

IS ANTI OXIDANT

WHICH WANTS TO PREVENT

OXIDATION OF FREE RADICAL

ISFREE RADICAL

WHICHATTACKS ANDDESTROYS THE BODY`S CELLS

IS OUR BODY WHICH

IS TRAPPED BY FREE RADICAL

Antioxidant

• Antioxidant is a molecule that inhibits theoxidation of other molecules.

• Oxidation reactions can produce free radicals. Inturn, these radicals can start chain reactions.When the chain reaction occurs in a cell, it cancause damage or death to the cell.

• Antioxidants terminate these chain reactions byremoving free radical intermediates, and inhibitother oxidation reactions.

• The lichens have played an important role as asource for new antioxidant agents.

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.

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)

• They do this by being oxidized themselves, so

antioxidants are often reducing agents.

• 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

• many research groups have driven efforts toassess the antioxidant properties of naturalproducts.

• 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

• 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

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

• 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