ANTIOXIDANT DEFENCE SYSTEM
Deepali Patekar Supriya Kheur Neeta Bagul Meena Kulkarni Aditi Mahalle Yashwant Ingle Varsha Dhas
Department of Oral Pathology & Microbiology,Dr. D.Y.Patil Dental College and Hospital, Pune, India
Corresponding Author:Deepali Patekar, Department of Oral Pathology,Dr. D.Y.Patil Dental College and Hospital, Pimpri, Pune-18,India.Ph- 09325311862. Email: [email protected]
Abstract
Several types of reactive species are generated in the body as a result of metabolic reactions in the form of free radicals .These species may be either oxygen derived or nitrogen derived and called prooxidants. They attack macromolecules including protein, DNA and lipid etc. causing cellular/tissue damage. To counter their effect, the body is endowed with another category of compounds called antioxidants. These antioxidants are produced either endogenously or received from exogenous sources and include enzymes like superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase, minerals like Se, Mn, Cu and Zn, and vitamins like vitamin A, C and E. In a healthy body, prooxidants and antioxidants maintain a ratio and a shift in this ratio towards prooxidants gives rise to oxidative stress. Human antioxidant defenses have evolved to protect biological systems against oxidative stress, and a sophisticated cooperative array of antioxidant defense mechanisms is found in biological systems.
of oxidative stress in the development and progression of various human diseases.
Key Words: Antioxidants, Free radicals, Superoxide dismutase (SOD), Catalase
The following article focuses on causes, role and conrol
Introduction e . g . c a t a l a s e ( C A T ) , g l u t a t h i o n e
peroxidase(GSH Px) A biological antioxidant may be
defined as a substance(present in low Chain breaking antioxidants that inhibit the concentrations compared to an oxidizable propagative phase of lipid peroxidation substrate) that significantly delays or eg superoxide dimutase(SOD),vitamin E, uric inhibits oxidation of a substrate. Substances acid.
that neutralize potential ill effect of free
Antioxidants according to their location
radicals are generally grouped in so called a 1,2,3,4
1. Plasma AO e.g. b-carotene, ascorbic Antioxidant defense system(ADS). Such a
acid, bilirubin,uric acid, ceruloplasmin, system encompasses many substances which
transferring. 2. Cell membrane antioxidants are often called by the generic names such as
e.g.a-tocopherol. 3. Intracellular antioxidants Antioxidants , Free radical scavengers , Chain
4,5
e,.g superoxide dimutase(SOD), catalase terminators or Reductants. Currently, a
(CAT),glutathione peroxidase(GSH Px). large number of antioxidants(AO) are being
6,7
investigated According to their nature and action
Antioxidant in biological system can be 1.Enzymatic-e.g.SOD,GSH Px,CAT
classified into:
2.Non enzymatic a) Nutrient AO e.g. 1 Antioxidant in relation to lipid
carotenoids, alfa-tocopherol, ascorbic acid, peroxidation:
selenium 2 Preventive AO : that will block the
ceruloplasmin albumin bilirubin transferring Flavanones- e.g.- Hesperitin 34
Flavones- e.g.- Chrysin ferrin uric acid
3 , Isoflavanoids- e.g.- Genistein A c c o r d i n g t o D a v i e s A D S
Anthocyanidins- e.g.-Cyanidin, Pelagonidin traditionally have be termed “primary” or
Phenolic Acid-“secondary”.
Hydroxycinnamic acids- e.g.- Ferulic, p-Primary defenses includes antioxidant
coumaric
compounds-Hydroxybenzoic acid –e.g.- Gallic acid, Ellagic A)Vitamin E,A,C and glutathione and uric
acid acid,
_ Gingerol B)AO scavenging enzymes such as SOD,CT
_ Curcumin and peroxidases.
For secondary defenses, he suggested 13,14,1516,17,18
Dietary sources of Antioxidants
lipolytic enzymes,phospholipases,proteolytic enzymes,proteases , peptidases, DNA repair
Vitamin C : Fruits (especially citrus) and
enzymes , endonuclease and ligase.
vegetables, including green and red peppers, Primary defenses interact with free tomatoes, potatoes, and green, leafy varieties
radicals generated directly from O2(namely (eg, spinach and collard greens). O2); secondary defenses scavenge radicals
arising from dismutation of O2. AO are also Vitamin E : Vegetable oils (eg, soybean, corn, classified as Extracellular AO and Intracellular and safflower) and vegetable oil products (eg, AO. SOD,catalase(CT) and glutathione margarine), whole grains, wheat germ, nuts peroxidase(GSH-Px)are not only distributed and seeds, and green, leafy vegetables.
in cytosol ,but are also localized in
mitochondria, where most of intracellular b-Carotene : Yellow-orange fruits (eg, 8,9
free radicals are produced cantaloupe) and vegetables (eg, carrots) and green, leafy vegetables.
The most important biological extracellular antioxidant are glutathione,
Polyphenolic Antioxidants : Tea, coffee,
v i t a m i n e - E , u r e a t , G S H - P x , S O D, C T,
soy, fruit, olive oil, chocolate, cinnamon, ceruloplasmin, and transferring. Although 19.
oregano and red wine considerable progress has been made in
identifying and understanding the mode of
Mechanism Of Antioxidants
action of ADS, complexity of intracellular
network of various antioxidants has impeded Free radicals are highly reactive understanding of overall protective efficacy molecules or chemical species containing one
10,11,12
of cytosolic defense system Also various or more unpaired electrons in their outermost antioxidants in plasma is crucial for shell. They react quickly with nearest stable maximum suppression of free radical reaction molecule to capture electron, in need to gain in extracellular compartment. stability. They promote beneficial oxidation that produces energy and kill bacterial
The various other non-enzymatic AO are
invaders. If free radicals are at reasonable Organosulfur compounds e.g-Allium, Allyl
levels, human body produces enzymes to sulfide, indoles
combat them and is helpful in immune system Antioxidant cofactors e.g.- Coenzyme O10
and anti bacterial cell activity. A single free Polyphenols –
radical can cause damage to millions of other
Flavonoids-molecules in body from functioning properly. Xanthones- e.g.- Mangostin
Flavonoids- e.g.- Quercein, Kaempferol This molecular destr uction is Flavanols- e.g.- Catechin, EGCG continually occurring in our body. Although
antioxidants are a result of breathing but these radicals such as copper and iron. free radicals attack us from many different
Role Of Enzymatic Antioxidants
sources every day. They are: Alcohol,
1. Catalase:
Tobacco, Drugs, Smoked and Barbecued Foods, Harmful Chemicals and Pesticides,
Chemically it is tetramer of four and Food Additives.
polypeptide chains containing four porphyrin
Antioxidant Defense heme groups which allow the enzyme to react
with hydrogen peroxide.Catalase is present in Antioxidant defense system (ADS)
high amounts in the liver , kidney and red against oxidative stress is composed of several
blood cells. In hepatocytes, peroxisomes lines and antioxidants are classified into four
exhibit high catalase activity as well as in 20
categories based on their function 21
microsomes and in the cytosol . Catalase is a
First: - Preventive antioxidants which major primar y antioxidant defense
suppress formation of free radicals. component which catalyze decomposition of 22 hydrogen peroxide into water and oxygen.
Second: - Radical scavenging antioxidants
Catalase the detoxify oxygen reactive radicals which suppress chain initiation and breaking
by catalyzing the formation of hydrogen chain propagation reactions.
peroxide which is derived from superoxide.
Third: - Repair and de novo antioxidants.
Fourth: - Adaption where the signal for the 2. Superoxide Dismutase
(SOD):-production and actions of free radicals
Depending on metal ion content induces formation and transport of the
SOD is grouped as:-appropriate antioxidant to the right site.
Cu/Zn SOD
The Antioxidant Process Mn SOD
Fe SOD Antioxidants block process of
oxidation by neutralizing free radicals. In The Activity of SOD appears to be doing so, antioxidants themselves become extracellular as well as intracellular seen in
oxidized. mitochondria and cytosolic compartment.
SOD activity differs in various tissues, highest
The two ways by which they act
are-levels are seen in liver, adrenal gland and
Chain-breaking
kidney and spleen. The SOD activity is When a free radical releases or steals regulated through biosynthesis, sensitive to
23
an electron, a second radical is formed. This tissue oxygenation It is found that in rats and molecule then turns around and does same yeast , biosynthesis of SOD is elevated when
24,25.
thing to a third molecule, continuing to subjected to high oxygen tension SOD is generate more unstable products. The process called primary defense as it removes the continues until termination occurs - either superoxide (O2-) radical ,repairs cell and radical is stabilized by a chain-breaking reduces damage by catalyzing the reduction of antioxidant such as beta carotene and vitamins superoxide anion to H2O2. Its catalytic C and E, or it simply decays into a harmless function was discovered by Mc Cord and
26
product. Fridovich
Preventive
3. Glutathione Peroxidase
(GSH-Px):-Antioxidant enzymes like superoxide
GSH-Px are classified as selenium dismutase, catalase and glutathione
dependent and selenium independent which peroxidase prevent oxidation by reducing rate
catalyses the reduction of hydrogen peroxides of chain initiation. They can also prevent
present intracellularly in the cytosol and and lipid peroxidation. The biological 27
antioxidant fuction of the selenium was mitochondrial matrix .GSH-Px protects
confined to its interaction enzyme GSH – PX against radical damage by reducing peroxides.
35 36
The role of GSH-Px in the inhibition of lipid . The amino acid selenocysteine is involved peroxidation were first reported by Mc Cay et in the synthesis of diverse selenoenzyme such
28
as glutathione peroxidase (reducing al Selenium dependent GSH-Px – associated
37,38
with membranes was reported by urshi and peroxides) iodothyronine deiodinases 2 9 , 3 0
(regulating thyroid hormone activity), and colleagues and is associated with
thioredoxin reductase. (regenerating d e g r a d a t i o n o f p h o s p h o l i p i d s
39,40,41
hydroperoxides. antioxidant systems) .
Role Of Non-enzymatic Antioxidants Selenium play important role to
replace sulphur in urethionine to form
Vitamin-E : Vit E represents two groups of selenomethionine, and gets incorporated into
42
c o m p o u n d s c a l l e d - To c o p h e r o l s proteins selenium contributes to its 4 3 , 4 4
and Tocotrienols Chemically tocopherols anticariog enic activity selenium have a saturated long phytyl tail attached to a concentration is found to be highest in chromane ring, whereas tocotrienols have a nucleus, followed by cytosol, mitochondria unsaturated phytyl tail. Isomers of and microsome. It has been hypothesized that tocopherols and tocotrienels differ from each selenium may act at the cellular level to other based on the degree of methylation of prevent the enzymatic conversion of
31
the chromane ring. There are eight structural precarcinogens to carcinogens. isomers alfa, beta, gamma, delta etc., among
An alternate possibility is that these, alfa - tocopherol is with the most
selenium enhances the detoxification process 32
potent Antioxidant activity . High levels of
of carcinogens substances and protects tocopherol are found in selected mammalian
against carcinogen induced chromosomal tissues such as liver, heart, testes and adrenal 45
damage glands. Intracellurlarly, Vitamin E is
associated with lipid rich membranes such as S e l e n i u m d e f i c i e n c y a l t e r s mitochondria and ER and therefore antioxidant defense systems by depressing
8
antioxidation property of tocopherol must be GSH Px in both liver and skeletal muscle and high in protecting against membrane lipid affects SOD & CAT activity
33 peroxidation .
Vitamin C (Ascorbic acid
):-Thus, as Vitamin E in Lipophilic in
It is hydrophilic scavenger of free character, it protects the unsaturated fatty
radicals and act as reducing and antioxidant agent. acids (PUFAS from peroxide, reacts and acts
It is essential for collagen, carnitine and neuro as a scavenger and gets itself oxidized to
transmitters' biosynthesis vit C works 34
quinone formed by free radicals Vitamin E is
synergistically with vit E and restores the
Essential for the membrane structure and 46
antioxidant properties of oxidized vit E integrity of Cell.
Ascorbic acid reserves both
Selenium 47,48,49
antioxidant and prooxidant . In the presence Selenium is thought to be as of transition metals like Fe3+ or Cu2+, vit essential micronutrient and it exerts benefial C/ascorbic acid generates oxygen free radicals
50,51,52
effects on health through is selenoproteins. thus induce lipid peroxidation . Synergistic The enzyme GPX is one of the most action of Vit C and E helps in inhibition of impor tant selenoproteins in which nitrosation from nitrite i.e. inhibits N-nitro contribution to the oxidatitive defence animal compound formation in heterogenous mixture
Vitamin A .4) Heffner, J. E., and J. E. Repine. Pulmonary strategies of antioxidant defense. Am. Rev.
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Conflict of Interest - None declared
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