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Review Article

Antioxidants: Enhancing oral and general health


Arvind Shetti, Vaishali Keluskar, Ashish Aggarwal
Department of Oral Medicine, Diagnosis and Radiology, KLE’S V. K. Institute of Dental Sciences, Belgaum, Karnataka, India

ABSTRACT
Free radicals and antioxidant therapy have attracted a great deal of attention in recent years. Antioxidants are compounds that
destroy the free radicals in the body, thereby preventing harmful oxidation-reduction reactions. Antioxidants are critical for
maintaining optimum health and well-being. The best sources of antioxidants are fruits and vegetables, which provide a variety of
antioxidants such as Vitamins A, C, E, and carotenoids. Currently available data are compatible with the notion that these vitamins
act as chemopreventives against some important cancers, e.g., carotenoids for lung cancer, ascorbic acid for salivary gland cancer,
tocopherols for head and neck cancers, etc. Thus, a greater consumption of fruits and vegetables should be encouraged as they are
the natural sources of these chemopreventive antioxidants along with other protective factors packaged by nature.

Key words: Antioxidants, beta carotene, free radicals, lycopene, oral cancer

DOI: 10.4103/0972-1363.57770
DOI

INTRODUCTION DISEASES CAUSED BY FREE RADICALS [FIGURE 1]

Antioxidants are substances that are capable of THE ANTIOXIDANT PROCESS


counteracting the damaging, but normal, effects of the
physiological process of oxidation in animal tissue. Antioxidants block the process of oxidation by neutralizing
Antioxidants are nutrients (vitamins and minerals) as well free radicals. In doing so, the antioxidants themselves
as enzymes (proteins in the body that assist in chemical become oxidized. Because of this, there is a constant need
reactions). to replenish our antioxidant resources. The effectiveness of
any given antioxidant in the body depends on which free
CONCEPT OF FREE RADICALS radical is involved, how and where it is generated, and the
target of damage. Thus, an antioxidant in one particular
Free radicals are chemically active atoms that have a system may protect against free radicals, while in another
charge due to an excess or deficient number of electrons. it could have no effect at all.
Free radicals containing oxygen, known as reactive oxygen
species (ROS), are the most biologically significant free CLASSIFICATION[5]
radicals. ROS include the radicals superoxide and hydroxyl.
Free radicals and other reactive oxygen species are derived TYPES OF ANTIOXIDANTS
either from normal essential metabolic processes in the
human body or from external sources such as exposure Vitamin E
to X-rays, ozone, cigarette smoking, air pollutants, and Vitamin E is the major antioxidant in all cellular
industrial chemicals. Because they have one or more membranes and it protects polyunsaturated fatty acids
unpaired electrons, free radicals are highly unstable. They against oxidation.[8] Because it is fat-soluble, it safeguards
cell membranes from damage by free radicals. Alpha-
scavenge the body to grab or donate electrons, thereby
tocopherol also protects the fats in low-density lipoproteins
damaging cells, proteins, and DNA.
from oxidation.

Vitamin C
Address for Correspondence
Correspondence: Dr. Arvind Shetti, Department of Oral
Medicine and Radiology, KLE’S V. K. Institute of Dental Sciences, Belgaum, Vitamin C scavenges free radicals that are in an aqueous
Karnataka, India. E-mail: shettiarvind01@rediffmail.com environment, such as inside the cells. It is believed to be

Journal of Indian Academy of Oral Medicine and Radiology / Jan-Mar 2009 / Volume 21 / Issue 1 1
Shetti, et al.: Antioxidants

Figure 1: Diseases caused by free radicals

the most important antioxidant in extracellular fluids and it cells). Beta-carotene is also especially used for scavenging
has many known intracellular activities as well.[8] Vitamin C free radicals in areas of low oxygen concentration.
works synergistically with Vitamin E to quench free radicals.
Selenium
Beta-carotene Selenium is a trace element. It forms the active site of several
Beta-carotene is the best quencher of singlet oxygen (an antioxidant enzymes including glutathione peroxidase.
energized but uncharged form of oxygen that is toxic to Similar to selenium, the minerals manganese and zinc
are trace elements that form an essential part of various
antioxidant enzymes.
ANTIOXIDANTS
ANTIOXIDANT-ENZYMES

ENZYMATIC NON-ENZYMATIC Superoxide dismutase, catalase, and glutathione peroxidase


serve as your primary line of defense [Chart 1] in destroying
Superoxide free radicals [Figures 2 and 3].
dismutase
Nutrient NonNutrient
Glutathione MECHANISM OF ACTION OF ANTIOXIDANTS
Peroxidase Alpha Ceruloplasmin
tocopherol Antioxidants neutralise free radicals by donating one of
Catalase
Transferrin their electrons, which ends the electron stealing reaction.
β- Carotene The antioxidant nutrient, however, does not become a free
Glutathione
reductase
Uric acid radical by donating an electron because they are stable in
Ascorbate
Peptides
either form. Important antioxidants include the following:
Glutathione Camosine
Glutathione
transferase Anserine 1. Chain breaking or scavenging ones, such as Vitamin E
Selenium (alpha tocopherol), Vitamin C (ascorbic acid), or
Vitamin A (beta carotene)
Chart 1: Antioxidants 2. Preventative antioxidants that function largely by

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fig 1 to be bw in print?????
Shetti, et al.: Antioxidants

sequestering transition metal ions and preventing present in tomatoes.[4] Lycopene has been hypothesized
Fenton reactions and are therefore largely proteins by to prevent carcinogenesis and atherogenesis by protecting
nature (e.g., albumin, transferring, or lactoferrin) critical cellular biomolecules, including lipids, lipoproteins,
proteins, and DNA.[1–3] In recent studies, serum and tissue
LYCOPENE levels of lycopene were shown to be inversely associated
with the risk of breast cancer, prostate cancer, coronary
Lycopene is one of the most potent antioxidants primarily heart disease,[7] and oral premalignant lesions. According

Figure 2: Fresh fruits-rich sources of antioxidants Figure 3: Green leafy vegetables/guard against free radicals

Figure 4: Tomatoes important source of lycopene Figure 5: Lycopene guard against oral cancer

Figure 6: Fruits and vegetables rich source of phytochemicals and


flavonoids Figure 7: Flavonoid in apple protect against lung cancer

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Shetti, et al.: Antioxidants

to various studies, lycopene, when given in the dosage of initial lesion or to prevent the development of a second
4–8 mg/day orally for 3 months,[6] leads to the reversal of or a separate primary
dysplastic changes in leukoplakia and when given in the
dosage of 16 mg/day[13] leads to substantials increase in ANTIOXIDANTS AND THE PREVENTION OF CANCER
the mouth opening in oral submucous fibrosis. Estimating
the daily intake of lycopene has been difficult due to the Antioxidants play a role in the later stages of cancer
variability of reported values in the food sources. On development. DNA damage is considered to be one of
average, the daily intake of lycopene is estimated to be 3.7 the most important contributors to cancer. Much of this
mg[12] [Figures 4 and 5]. damage is oxidative in nature. Antioxidants may be able
to cause the regression of premalignant lesions or inhibit
BETA CAROTENE their development into cancer. Preliminary studies have
indicated that some antioxidants, particularly ß-carotene,
The carotenoids are a group of red, orange, and yellow may be of benefit in the treatment of precancerous
pigments found in fruits and vegetables.[8] These include conditions such as oral leukoplakia, which may be a
b-carotene (carrots), lycopene (tomatoes), and lutein precursor to oral cancer.[8] Some antioxidant nutrients may
(spinach).[11] Carotenes have an excellent property of protect against cancer through mechanisms other than their
free radical trapping, especially peroxyl and hydroxyl antioxidant properties. For example, carotenoids may both
radicals, which are involved in the genesis of cancers enhance immune function and increase gap junctional
and aging. Beta carotene also increases cell mediated communication (a type of interaction between cells that
immune responses due to increased monocyte expression inhibits cell proliferation); both of these actions may be
and increased activity of the tumor necrosis factor alpha. relevant to cancer prevention.[8] In general, high intake
Serum beta carotene levels have been shown to decrease of fruits and vegetables are associated with a protective
in various oral premalignant lesions and conditions and its effect against cancer. Both biochemical and epidemiologic
supplementation (30 mg/day) [16] have led to the regression studies have indicated that antioxidant nutrients may have
of the lesions. important protective effects in the prevention of human
cancer [Figure 8].
PHYTOCHEMICALS
PROTECTIVE ROLES OF MICRONUTRIENTS IN
These are non nutrient compounds that have biological
activity inside the human body. They provide colors,
CARCINOGENESIS[18]
taste, and aromas to the fruits and vegetables. They mimic
Nutrients and their functions
hormones and suppress the development of diseases.
1. Beta-carotene
Phenolic compounds such as flavonoids have been
Precursor of Vitamin A
demonstrated to have anti-inflammatory, anti-allergenic,
Anti-oxidant and free radical scavenging
anti-viral, anti-aging, and anti-carcinogenic activity.[9,10] In
Immunomodulation, stimulation of increase in the
addition to an antioxidant effect, flavonoid compounds may
numbers of T-helper and NK cells as well as cells with
exert protection against heart disease through the inhibition
IL-2 receptors
of cyclooxygenase and lipoxygenase activities in platelets
and macrophages[10] [Figures 6 and 7].

THERAPEUTIC USE OF ANTIOXIDANTS FOR ORAL


LESIONS
The possible uses of antioxidants for oral mucosal lesions
include the following:

1. Prevention of lesions in high-risk individuals with


mucosa that clinically appears normal with no history
of either premalignant or malignant lesion
2. The treatment of premalignant oral lesions
3. In patients who have had either premalignant or
malignant oral lesions that have been successfully
treated, in order to prevent recurrence of the treated Figure 8: Carcinogenesis and chemoprevention

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Shetti, et al.: Antioxidants

Inhibition of mutagenesis food processing, availability, and cost of the particular


Inhibition of cancer cell growth antioxidant before prescribing it to the patient.

2. Vitamin A (retinoids) CONTROVERSIAL AREAS IN ANTIOXIDANTS THERAPY


Inhibits keratinization and terminal differentiation of
epidermal cells Current literature reports that a half century of data
Enhancement of cellular immunity demonstrates the lack of predictability of antioxidant therapy
Arrest/reverse leukoplakia progression and it has not been validated by the scientific method.
Induction of cytotoxic and cytostatic effects on cancer Widespread use of antioxidants has failed to quell the
cells current pandemic of cancer, diabetes, and cardiovascular
Influence DNA, RNA, and gene expression disease or to stop or reverse the aging process. Antioxidant
Interfere with carcinogenic stimulation and binding therapy in human reproductive medicine is controversial.
High doses of Vitamin A may have embryotoxic and
3. Vitamin E (A-tocopherol) teratogenic effects.[14] Large doses of ascorbic acid may be
Free radical scavenging associated with the inhibition of ovarian steroidogenesis
Maintenance of membrane integrity, immune function and increased probability of abortion.[15]
Inhibition of cancer cell growth/differentiation
Cytotoxicity CONCLUSION
Inhibits mutagenicity and nitrosamine formation
Inhibition of DNA and RNA, protein synthesis in cancer Protection against free radicals can be enhanced by an
cells ample intake of dietary antioxidants, of which the best
studied are Vitamin E, Vitamin C, and carotenoids.
4. Vitamin C (ascorbic acid) Substantial evidence indicates that foods containing
Anti-oxidant antioxidants and possibly in particular the antioxidant
Reduces vitamin E degradation nutrients may be of major importance in disease prevention.
Enhances chemotaxis, phagocytosis, collagen synthesis Efforts should be made to ensure an optimum intake of
Inhibits nitrosamine formation foods containing these important molecules. Finally, it can
Enhances detoxification via cytochrome P450 be concluded that the following sayings ring true:
Blocks formation of fecal mutagens
Reduces oncogene expression “REACH FOR A CARROT BEFORE CANCER REACHES
YOU”
EFFICACY OF A MIXTURE OF ANTIOXIDANT VITAMINS and
“A CARROT A DAY KEEPS CANCER AWAY”
Individual antioxidant vitamins produce varying degrees of
tumor regression only at very high doses, which frequently REFERENCES
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