ANTIOXIDANTS IN HEALTH ANTIOXIDANTS IN HEALTH

AND DISEASEAND DISEASE

• Changes in life style and the modern day eating habits has been a major source of worry to all the health workers worldwide.

• Junk food and the so called fast food is leading to an increase in the incidence of heart diseases .

• Antioxidants have come to the picture in a big way as agents to help protect us from various diseases and also in maintaining a healthy internal cellular environment

INTRODUCTIONINTRODUCTION

• In recent years a lot of research has gone into finding ways and products to prevent diseases like cardiovascular diseases , to prevent the harmful effects of the sun rays , promoting the health status of people with HIV .

• Antioxidants are not only helping us protect ourselves from these diseases but also the research being undertaken in this field also is helping us understand the pathophysiology behind these diseases.

INDEXINDEX

• BASIC INTRODUCTION TO ANTIOXIDANTS

• FREE RADICALS

• OXIDATIVE STRESS

• VARIOUS ANTIOXIDANTS

• SOME MORE FACTS ABOUT ANTIOXIDANTS

• CONCLUSION

• REFERENCES

ANTIOXIDANTANTIOXIDANT

• An agent that prevents or inhibits oxidation.

• Antioxidants are substances that may protect cells from the damaging effects of oxygen radicals, highly reactive chemicals that play a part in atherosclerosis, some forms of cancer.

FREE RADICALSFREE RADICALS

• These are highly reactive and unstable molecules having an unpaired electron in their outermost shell

• Can exist independently

• Produced during oxidation of a substrate

• Cause oxidative damage to various

biological materials

• Generation of reactive oxygen species

causes cascading oxidative tissue damage

for e.g. – to muscle cells, artery walls

EXAMPLES OF FREE RADICALSEXAMPLES OF FREE RADICALS

– SUPEROXIDE ANION Ö2

– HYDROGEN PEROXIDE H2O2

– HYDROXYL RADICAL OH-

- POLLUTANTS • EG. CIGARETTE SMOKE,

SMOG,JUNK FOOD(NUTRTIONAL POLLUTANTS)

OXIDATIVE STRESSOXIDATIVE STRESS

• Oxidative stress is a state of being when the balance between pro-oxidants and anti-oxidant levels is shifted towards pro-oxidants

• Oxidative stress has been recognized as a key

mechanism in the development of vascular damage, particularly atherosclerosis.

ANTIOXIDANTSANTIOXIDANTS

• vitaminsflavinoids

amino acids

lipid-lowering agents

monounsaturated fats

beta-carotene

herbs

ACTIONS ACTIONS • Antioxidants have protective mode of action

-Donate 1 electrons (e-)

– E- intercept free radicals • Mop them up

– Convert them into less reactive molecules• Neutralize the free radicals• Protect other substances from damage

• Act as ‘bodyguards’ & sacrifice themselves

• antioxidants can be REACTIVATED– by receiving electron(s)

• ie. antioxidants are RECYCLED

• more than 400 compounds display anti-oxidant potential

• elaborate antioxidant defence systems…– protects cells from free-radical attack

ANTIOXIDANT DEFENCE SYSTEMSANTIOXIDANT DEFENCE SYSTEMS

• 1. Endogenous antioxidant defence system

– Superoxide dismutase

– Catalase

– Glutathione peroxidase

• 2. Antioxidants provided from dietary intake– Selenium– Iron– Copper– Zinc– Manganese– Vitamins (a, c & e)– Polyphenols– Alcohol

– Act as enzyme co-factors

FREE RADICAL SCAVENGER SYSTEMSFREE RADICAL SCAVENGER SYSTEMS

• Since free radicals initiate lipid peroxidation , body has devised ways to remove free radicals

A) enzymatic free radical scavenger system (EFRSS) :it consists of antioxidant enzymes like superoxide dismutase , glutathione-e-transferase,catalase peroxidase and glutathione peroxidase

B) non_enzymatic free radical scavenging system (NEFRSS): it consists of several compounds , which act as antioxidants . they include glutathione, melatonin, tocopherol, ascorbic acid, lipoic acid, uric acid , carotenes , caffeine and bilirubin

PROTECTION AGAINST OXYGEN PROTECTION AGAINST OXYGEN RADICALS IN BIOLOGICAL SYSTEMSRADICALS IN BIOLOGICAL SYSTEMS

• REFERRED TO AS THE SUPEROXIDE THEORY OF OXYGEN TOXICITY

A) PROTECTION BY ENZYMES:

CATALASE

2H2O2 2H2O + O2

PEROXIDASE

SH2 + H2O2 S +2H2O

(SH2 IS THE SUNBSTRATE BEING OXIDISED

• Catalase is present in all major organs , particularly in the liver, and red cells, and in modest amounts in the brain , heart and skeletal muscles

• Superoxide dismutase: the enzymes are an essential defence mechanism against the superoxide radical .

• Protection in also offered by copper-zinc containing enzymes and manganese containing enzymes

• PROTECTION BY SMALL MOLECULES:

This category includes molecules like ascorbic

Acid, glutathione , uric acid.

CLASSES OF ANTIOXIDANTSCLASSES OF ANTIOXIDANTS• FALL IN 2 CLASSES

A- preventive antioxidants , these reduce the rate of chain initiation and include catalase and other peroxidases that react with rooh and chelators of metal ions such as EDTA and DTPA

B- chain breaking antioxidants, these interfere with chain propagation and include superoxide dismutase and vitamin E

CLASSIFICATION OF ANTIOXIDANTSCLASSIFICATION OF ANTIOXIDANTS

• ACCORDING TO THE WAY THE ANTIOXIDANTS ACT

A) Preventive antioxidants: these suppress the formation of free radicals for example superoxide dismutase, catalase, glutathione peroxidase,carotenoids, transferin , albumin

B) radical-scavenging antioxidants: scavenge radicals to inhibit chain initiation and break chain propagation for example vit a, vit c, vit e, uric acid

C) repair and de novo enzymes that repair the damage and reconstitute membranes . for example DNA repair enzymes, lipase, protease,transferase

SYNTHETIC ANTIOXIDANTSSYNTHETIC ANTIOXIDANTS

• THESE ARE WIDELY USED AS PRESERVATIVES OF PROCESSED FAT AND FOODS

• THEY INCLUDE BUTYLATED HYDROXY TOLUENE(BHT) , BUTYLATED HYDROXY ANISOLE(BHA) AND PROPYL GALLATE(PG)

VITAMIN A (RETINOL AND BETA-VITAMIN A (RETINOL AND BETA-CAROTENE)CAROTENE)

• VITAMIN A • (RETINOL AND Β-CAROTENE)

• Similar action to vitamin E, particularly in lung tissue

– Protection against viral/bacterial lung infection?

– Not in megadoses• Possible causative effect in lung cancer

• Beta carotene is a water soluble precursor to vitamin A, and is a antioxidant in itself; where vitamin a has no antioxidant activity.

FOUND IN:CORN, SQUASH AND

CARROTS, EGG YOLK, AND OTHER PIGMENTED FRUITS AND VEGETABLES. THIS IS WHAT HELPS GIVE THEM THEIR YELLOW COLOR.

• THERE ARE SEVERAL CREDIBLE REASONS FOR HYPOTHESIZING THAT BETA-CAROTENE MIGHT REDUCE THE RISK OF CANCER

1 increased consumption is associated with a reduced risk

2 as an antioxidant it inhibits the early stages of carcinogenesis

DEFICIENCY AND TOXICITYDEFICIENCY AND TOXICITY

• Deficiency of vitamin A causes blindness• Earliest sign includes sensitivity to green light• A more prolonged deficiency leads to xerophthalmia characterized

by keratinization of cornea , skin and finally blindness

Toxicity

Excessive unbound vitamin causes toxicity.

Symptoms include head ache , nausea , ataxia and

anorexia, hepatomegaly and hyperlipidemia, hypercalcemia and calcification of soft tissues .

VITAMIN CVITAMIN C

• Gives up electrons very easily when they are needed.

• Helps to reactivate vitamin E

• Unique that they can then receive them again to become reactive, having the ability to recycle themselves over and over again.

• Protects oxygen and iron from oxidation.

• Protects against oxidation stress. • Helps with connective and epithelial tissue maintenance and repair. • Helps protect arteries against oxidative damage.• Water soluble and can flush out of the body readily, about 24-48

hour body retention before excreted.

RDA:Men = 90 mg/dayWomen = 75

mg/day

• Vitamin c inhibits the chemical synthesis of nitrosamines (most of which are animal carcinogens) in gastric content

• This however occurs only intakes of a 1000mg

• Research evidence suggests that intake of vit c much higher than the RDA may reduce the risk of chronic heart diseases and cancer especially when combined with higher intakes of Vit E

VITAMIN C AS COENZYMEVITAMIN C AS COENZYME

• Acts as a coenzyme for 2 hydroxylases

• Copper containing hydroxylases (dopamine beta

hydroxylase, peptidyl glycine hydroxylase)

• Iron containing hydroxylases (proline and lysine hydroxylases, aspartate beta-hydroxylase, trimethyllysine and gamma- butyrobetaine hydroxylases)

ADVERSE EFFECTS OF VITAMIN CADVERSE EFFECTS OF VITAMIN C

• Most hypothetical adverse effects cited for decades (except for mild and transient GI effects) seem to have little or no factual known basis

• Some of the reported adverse effects include conditioned scurvy, oxalate kidney stones, excessive iron absorption or release (pro-oxidant effect), GI distress

VITAMIN EVITAMIN E

• Fat-soluble antioxidant• Absorbed in small

intestines• Primary defender against

effects of free radicals in the body

• Protects cell membranes• Stored in liver and fat

cells.• Protects components of

the cell and their membrane from destruction

Shown to protect against LDL oxidation, raises HDL, lowers total cholesterol and improves blood pressure.

A MAJOR LIPID SOLUBLE ANTIOXIDANTA MAJOR LIPID SOLUBLE ANTIOXIDANT

• Vit E is a major lipid soluble antioxidant in cell membranes and plasma lipoproteins

• Acts as a chain-breaking , free radical trapping antioxidant

• Reacts with lipid peroxide radicals formed by peroxidation of PUFA before they can establish a chain reaction

• The tocopheroxyl free radical formed is un-reactive

REGENERATION OF TOCOPHEROLREGENERATION OF TOCOPHEROL

• The tocopheroxyl free radical is reduced back to tocopherol by reaction with vitamin c in plasma

• The resultant monodehydroascorbate free radical formed undergoes enzymic or non enzymic reaction to yield ascorbate and dehydroascorbate

PROOXIDANT ACTIONPROOXIDANT ACTION

• The relative stability of the tocopheroxyl radical formed means that it can penetrate deeper into cells and potentially propagate a chain reaction

• This occurs usually at high concentrations of Vit E in the blood

• Protects cell membranes• RDA men = 15mg/day• RDA women = 15 mg/day• Tissues in the cells exposed to

the highest amounts of oxygen like mitochondria seem to have the highest amount of vitamin E

ATHEROSCLEROSISATHEROSCLEROSIS

VITAMIN E AND HEART DISEASEVITAMIN E AND HEART DISEASE

• Several research approaches have shown protective effects of vitamin e on heart disease is associated with intakes well above the RDA

• LDL oxidation decreases significantly in blood taken from subjects receiving more than 400 IU per day but not less than 200 IU/ day

• One study revealed no beneficial affect on heart disease from a supplement of 50 mg given for 5 -7 days to middle aged Finnish men who were long term heavy smokers

SELENIUMSELENIUM

• AN ESSENTIAL TRACE MINERAL, RDA OF 70 UG/DAY.

• Found in glutathione peroxidase which is a free radical scavenging enzyme that contains selenium. It destroys peroxides and thus protects lipid membranes as does vitamin E

SOURCES OF SELENIUMSOURCES OF SELENIUM

• Plant foods are the major source • Depends on the amount of selenium in the soil• Found in meat and sea food also in animals which eat

grain or plants• Sources include brazil nuts, tuna, beef, spaghetti, cod,

turkey cottage cheese, oatmeal, chicken breast, macaroni, rice, bread, walnuts, bread

RDA FOR SELENIUMRDA FOR SELENIUM

AGE MALES AND FEMALES

PREGNANCY LACTATION

1-3 YRS 20 MICRO/DAY N/A N/A

4-8 YRS 30 MICRO/DAY N/A N/A

9-13 YRS 40 MICRO/DAY N/A N/A

14-18 YRS 55 MICRO/DAY 60 MICRO/DAY 70 MICRO/DAY

19 YRS + 55 MICRO/DAY 60 MICRO/DAY 70 MICRO/DAY

SELENIUM AND CANCERSELENIUM AND CANCER

• Observational studies indicate that death from cancer, including lung cancer , colorectal , and prostrate cancer , is lower among people with higher blood levels or intake of selenium

• Selenium affects cancer in two ways.

1 – as an anti-oxidant by protecting from the harmful effects of free radicals

2 some of the breakdown products of selenium are believed to enhance immune cell activity and suppressing blood vessel development to the tumor

SELENIUM AND ARTHRITISSELENIUM AND ARTHRITIS

• Surveys indicate that individuals with Rheumatoid arthritis , have reduced selenium levels in their blood.

In addition , some individuals with arthritis have lower selenium intake .

selenium, as an antioxidant , may help relieve symptoms of arthritis by reducing the free radical levels

SELENIUM AND HEART DISEASESSELENIUM AND HEART DISEASES

• Surveys suggest that oxidative stress from free radicals may promote heart disease

• Oxidized form of LDL promotes plaque build up in coronary arteries

• Selenium may help in reducing the oxidation of LDL and thus preventing plaque build up

SELENIUM AND HIVSELENIUM AND HIV

• Selenium deficiency results in decreased immune cell counts, increased disease progression , and high risk of death.

• Oxidative damage may further contribute to damage of immune cells

SELENIUM TOXICITYSELENIUM TOXICITY

• Levels more than 100 micrograms/deciliter can result in selenosis

• Symptoms include GI upset, hair loss, white blotchy nails , garlic breath odor, fatigue, irritability and mild nerve damage

ROLE OF SELENIUM IN THYROID ROLE OF SELENIUM IN THYROID HORMONE METABOLISMHORMONE METABOLISM

• Type-i tryiodothyronine 5-deiodinase is a selenium containing enzyme.

• This explains the impairment of thyroid hormone metabolism caused by selenium deficiency in animals with normal Vit E status

• A further consequence of the role of selenium in thyroid hormone metabolism is the exacerbation of some of the thyroid changes in iodine deficiency by a concurrent selenium deficiency

Oligomeric ProanthocyanidinsOligomeric Proanthocyanidins(Bioflavanoids)(Bioflavanoids)

• 20 times stronger antioxidant then Vitamin C and 50 times stronger then Vitamin E.

• Water soluble

• Ability to attach to cells and their proteins for up to 72 hours protecting them from oxidation and free radical damage.

• Able to cross the blood-brain barrier

• Detoxifier• Replenishes antioxidant effect of eye fluid, which help protect the

eye against uv rays.

• FOUND IN: GRAPE SEED, RED WINE, PINE BARK (PYCNOGENOL), GRAPE SKIN, PEANUT SKIN, AND SOME WHITE WINES AND FRUITS.

Flavanoids Flavanoids

• Sometimes referred to as “super antioxidants.”• Shown to have: antiviral, anti allergic, anti inflammatory, anti

thrombogenic and anti carcinogenic effects.• Scavenge for free radicals associated with oxygen and iron; or by

inhibiting oxidative enzymes.• Over 4000 flavanoids have been found, fall in four different groups:

flavones, flavanones, catechins, and anthocyanins.

FOUND IN: CERTAIN FRUITS, FLOWERS, ROOTS, STEMS, TEA, WINE, GRAINS AND VEGETABLES.

BASIC STRUCTURE OF FLAVINOIDSBASIC STRUCTURE OF FLAVINOIDS

PHYTOCHEMICALSPHYTOCHEMICALS

• Non-nutrient compounds found in plant-derived foods that have biological activity in the body.

• Contribute to food taste, aromas, colors and other characteristics.

• Act as antioxidants, mimicking hormones, and suppressing the development of diseases.

• Work better when combined with other phytochemicals.

Other effects of PhytochemicalsOther effects of Phytochemicals

• May help prevent the introduction of some cancers• Block/neutralize enzymes which promote cancer &

other diseases• May help keep cholesterol in check• Decrease blood clot formation• May help prevent osteoporosis

SOME MORE FACTS ABOUT SOME MORE FACTS ABOUT ANTIOXIDANTSANTIOXIDANTS

ANTIOXIDANT ENZYME LEVELS IN ORAL ANTIOXIDANT ENZYME LEVELS IN ORAL

SQUAMOUS CELL CARCINOMASQUAMOUS CELL CARCINOMA • In a recent study semi quantitative immuno-

histochemistry was used to examine 26 archived oral squamous cell carcinoma biopsies.

• Results showed that basal cells displayed lower anti-oxidant enzyme levels than spinous cells , and primary tumor cells showed lower antioxidant enzyme staining intensities than did their normal counterparts.

OXIDANT AND ANTIOXIDANT ACTIVITY OXIDANT AND ANTIOXIDANT ACTIVITY CHANGES IN PATIENTS WITH ORAL CANCER CHANGES IN PATIENTS WITH ORAL CANCER

AND TREATED WITH RADIOTHERAPYAND TREATED WITH RADIOTHERAPY• In oral cancer, radiotherapy may be used as the sole

treatment or in combination with other modalities.

• Study done in oncology department ,Bernard institute of radiation and oncology , Chennai medical college, Chennai , India.

Radiation induces lipid peroxidation by inactivating the antioxidant enzymes, thereby rendering the system inefficient in management of the free radical attack. Thus, the degree of radiation affects the extent of the depression of the antioxidant enzyme activities and increases lipid peroxidation

• THE ACTIVITIES OF RED BLOOD CELL

HEMOLYSATE ANTIOXIDANT ENZYMES SUCH AS SOD , CATALASE ,GPX, GR, GST AND G6PDH SHOWED A SIGNIFICANT DECREASE , REPRESENTING THE LACK OF ANTIOXIDANT

ANTIOXIDANTS IN WOUND HEALING ANTIOXIDANTS IN WOUND HEALING AND SCAR FORMATIONAND SCAR FORMATION

• IN A RECENT STUDY CONDUCTED BY F.A.D.T.G WAGENER IN THE DEPARTMENT OF PHARMACOLOGY AND TOXICOLOGY ,RADBOUD UNIVERSITY NIJMEGEN MEDICAL CENTRE, NIJMEGEN CENTRE FOR MOLECULAR SCIENCES , NETHERLAND,

It was shown that cur cumin treatment in high doses (>25 micro m) may provide a novel way to modulate pathological scar formation through the induction of fibroblast apoptosis, while antioxidant molecules (ho) act as fine tuning molecules

Reduction of collagen degradationin experimental granulation

tissue by vitamin E and selenium• STUDY DONE BY• B. Asman^-^ P. Wijkander^ and A. Hjerpe^ Departments of 'Periodontology, ^Clinical Chemistry I and

^Pathology II, Karolinska Institute, Huddinge University Hospital, S-141 86 Huddinge, Sweden

• Study revealed that by administering pharmacological doses of both vitamin E and selenium sub cutaneousiy and by injection into sponges implanted sub cutaneously ,this breakdown of collagen was reduced. Vitamin E and selenium are potential inhibitors of the free oxygen radicals from phagocytic inflammatory cells. It is therefore suggested that these radicals may play a role in the collagen destruction by granulation tissues, as in periodontitis.

ANTIOXIDANT CAPACITY OF SALIVAANTIOXIDANT CAPACITY OF SALIVA

• Pro-oxidant and antioxidant features of saliva

Saliva contains many biochemical systems known to be

involved in soft-tissue repair, and many antibacterial

components including lysozyme, lactoferrin and

salivary peroxidase. Human whole saliva contains a

complex peroxidase system, the major components of

which include different forms of lactoperoxidase

secreted by the salivary glands and myeloperoxidases

from PMN.

• Salivary peroxidase catalyses the peroxidation of

The thiocyanate ion to generate oxidation

products that inhibit the growth and

metabolism of many micro-organisms (tenovuo et

al.1986, Pruitt et al. 1986).

ANTIOXIDANT STATUS OF ORAL MUCOSAL ANTIOXIDANT STATUS OF ORAL MUCOSAL TISSUE AND PLASMA LEVELS IN SMOKERS TISSUE AND PLASMA LEVELS IN SMOKERS

AND NON SMOKERSAND NON SMOKERS

• Antioxidant status is thought to be important in the development of potentially malignant oral lesions and oral squamous cell carcinoma.

• A study done by C.G COWAN et al

• The researchers found that smokers were found to have significantly lower levels of plasma beta-carotene and tissue alpha carotene than non smokers

LEVELS OF LIPID PEROXIDES AND ANTI-OXIDANTS IN LEVELS OF LIPID PEROXIDES AND ANTI-OXIDANTS IN SMOKERS AND NON-SMOKERSSMOKERS AND NON-SMOKERS

• In a study done in KGMC LUCKNOW, India, it was found out that smokers who smoked more than 50 cigarettes a day had higher levels of lipid peroxides and lower levels of antioxidants in their plasma

Plasma antioxidant levels in chronic cholestatic liver diseases

• A STUDY DONE BY A. FLOREANI, A. BARAGIOTTA, D. MARTINES, R. NACCARATO & A.

D'ODORICO Department of Surgical and Gastroenterological Sciences, University of

Padova, Italy This study showed that all though clinical evidence of deficiencies , plasma

levels of antioxidants are low in patients with cholestatic diseases even in the initial stage of the disease.

• This is probably due to mal-absorption of fat-soluble vitamins, as well as other mechanisms of hepatic release

,suggesting the need for dietary supplementation.

VITAMIN C PREVENTS CIGARETTE SMOKE INDUCED OXIDATIVEDAMAGE OF PROTEINS AND INCREASED PROTEOLYSIS

• Aqueous extracts of cigarette smoke contains some stable oxidants which oxidize human plasma proteins, bovine serum albumin, amino acid homopolymers, and also cause extensive oxidative degeneration of microsomal proteins

• Ascorbate almost completely prevents cigarette smoke induced oxidation and thereby protects the microsomes from subsequent protein degradation

INFUENCE OF ORAL ANTIOXIDANTS ON ULTRAVIOLET RADIATION-INDUCED SKIN DAMAGE

IN HUMANS

Human supplementation studies examining the potential of a range of oral agents to protect against UV r-induced skin effects show mixed results ;further studies should examine whether certain sub groups of the population may show augmented benefits

REACTIVE OXYGEN SPECIES AND REACTIVE OXYGEN SPECIES AND INFERTITLITYINFERTITLITY

CONCLUSIONCONCLUSION

• Antioxidants act in more ways than one in protecting the internal environment of the body from free radicals .

• Without them total chaos would ensue and the body system would get completely deranged.

• All though a lot of research has gone into this arena of health care but still a lot is needed for us to finally be able to accurately use them as therapeutic agents

REFERENCESREFERENCES

• Harpers illustrated biochemistry – 26”th edition• Discovering nutrition –Insel Turner Ross• Nutrition- Concepts and controversies-SIZER , WHITNEY -7”th

edition• Dental hygienists guide to nutritional care – Dairs Stegiman• Principles of Biochemistry –LEHNINGER, NELSON, COX-2”nd

edition• Introduction to human nutrition-Gibney, Vorster , Kok• Principles of human nutrition- Eastwood -2”nd edition• British journal of clinical pharmacology-2006-Pietro Minuz, Cristiano

Fava & Luciano Cominacini

• Journal of internal medicine-2000- J. T. SALONEN1 et al.

• ORIGINAL ARTICLE BY A. Scharstuhl1 et al -2008

• Journal of clinical periodontology- Battino M et al.-2002

• Journal of oral pathology and medicine -Cowan CG et al-1999

• Journal of periodontal research- Garg N et al. -2006

THANK YOUTHANK YOU