Antioxidants in Dentistry

INTRODUCTION

An antioxidant is a molecule which inhibits oxidation reaction. Antioxidants terminate the chain reaction caused by free radicals of oxidation reaction, preventing cell damage or death of the cells. Insufficient levels of antioxidants or inhibition of antioxidant enzymes causes oxidative stress and damage or kill the cells. It has been suggested that negative effects of nicotine are reversed by antioxidants1. The oral cavity is under constant bombardment from foods and drinks, as well as substances such as alcohol, tobacco products and nicotine, dental materials and much more. Bacteria and other disease-causing agents along with systemic conditions present further insult. Because the oral tissues are delicate, they are especially vulnerable to cell damage caused by free radicals and oxidative stress2. Maintaining a good balance of oxidants and antioxidants is very essential for maintaining oral health. Factors such as pollutants, alcohol, nicotine, substances used in dental procedures can disturb the balance of oxidants in oral tissues. Antioxidants help to offset this imbalance3. Antioxidants are molecules that inhibit oxidation of other molecules, thereby preventing formation of free radicals. These free radicals can cause harmful chain reactions that are responsible for cell damage or cell death, which in turn lead to carcinogenesis4. Antioxidants neutralize these radicals by donating their electrons there by ending the electron taking reaction5. As an alternative medicine, herbal therapy is a treatment modality to remedy many medical and dental conditions6. Antioxidants have also been used in combination with dried, fresh, and blended herbal paste7. The majority of herbal supplements include green tea catechins, aloe vera, star anise oil, myrrh gum, calendula extract, ammonium glycyrrhizate (from liquorice root), fennel oil, and neem extracts8. Most recently, dental manufacturers and distributors have incorporated antioxidant supplements into toothpastes, mouth rinses/mouthwashes, lozenges, fluoride gels and dentifrices, oral sprays, breath fresheners, and other dental products for the control of gingival and periodontal diseases. Antioxidants are taken systemically, such as foods and vitamin supplements, topical antioxidants may have an effect on oral cells.9 The success of topical antioxidants on skin cells suggests perhaps a similar effectiveness of topical compounds on cells in the oral cavity. Research studies are currently under way to examine the effectiveness of combinations of antioxidants applied topically to oral cells.10 An increased interest in the role of free radical’s oxidative damage in human diseases along with upsurge research implies its potential in dental practice too. They are used as an adjunct to various other modalities in the treatment of oral premalignant lesions and conditions such as leukoplakia, lichen planus, oral sub mucous fibrosis and oral cancer etc11. Antioxidant properties of vitamins aid in the prevention of progression of premalignant lesions and conditions into fulminant oral squamous cell carcinoma.12 Antioxidant has been proposed useful in the chemoprevention and management of various precancerous lesions and other free radicals related diseases13. Many fantastic claims have been made about antioxidants for cancer prevention, decreasing cardiovascular diseases, even slowing down the process of aging. Overall, the strong positive values associated with antioxidant and the frightening qualities attributed to free radicals have clearly increased the interest in using antioxidant supplement.14

DEFINITION

The definition proposed by the panel on Dietary Antioxidants and Related Compounds of the Food and Nutrition Board:

“A dietary antioxidant is a substance in foods that significantly decreases the adverse effects of reactive oxygen species, reactive nitrogen species, or both on normal physiological function in humans.” 18

HALLIWELL (2007) gave a more specific definition, stating that an antioxidant is “any substance that delays, prevents or removes oxidative damage to a target molecule”. 20

NATURAL ANTIOXIDANTS IN DENTISTRY

Antioxidants are being widely used in routine general clinical practice. An increased interest in the role of free radical oxidative damage in human diseases along with an upsurge in research implies its potential in dental practice too.1 Consumption of antioxidant supplements in developed countries has become widespread with about one third of adults being ‘addicted' to them. However, dental research field has not focused in the safety and efficacy of the antioxidants. Anti-oxidants are naturally available in green tea, spinach, citrus fruits, legumes, green vegetables, turmeric, clove, blue green microalgae, papaya, mango, cocoa, tomato, and cranberry.2

RETINOIDS

Retinoids are the natural and synthetic derivatives of vitamin A. The retinoids in the body originate from retinyl esters, carotenoids, and retinal in diets. The effects of retinoids are mediated by scavenging effect (traps peroxyl free radicals in tissue at low partial pressure of oxygen).3

L-ASCORBIC ACID (VITAMIN C)

L-ascorbic acid (L-AA), the so-called vitamin C has antioxidizing properties and reacts with superoxide produced as a result of the cells normal metabolic processes; this inactivation of superoxide inhibits the formation of nitrosamines during protein digestion and helps avoid damage to DNA and cellular proteins. LAA apart from being antioxidant also has following actions enhances chemotaxis, phagocytosis, collagen synthesis, blocks formation of faecal mutagens, reduces oncogene expression. 3

TOCOFEROL (VITAMIN E)

Tocopherol is the commonest and most active form of vitamin E. Tocopherol is an effective antioxidant at high levels of oxygen, protecting cellular membranes from lipidic peroxidation, free radical scavenging, maintenance of membrane integrity and immune function. 4

LYCOPENE

The prominent carotenoid in serum is the antioxidant red pigment called lycopene which is fat soluble. Lycopene has been hypothesized to prevent carcinogenesis especially in upper digestive tract neoplasm and atherogenesis by protecting critical cellular biomolecules, including lipids, lipoproteins, proteins, and DNA. Lycopene has the unique feature of getting bound to chemical species that react to oxygen, thus being the most efficient biological antioxidizing agent.4

CATECHINS / POLYPHENOLS

The tea leaves contain Retinoid Acid Receptors (RARs) and Retinoid X Receptors (RXRs). Recently, retinoids have been implicated in the induction of cell death in many tumor-derived culture cell systems in both retinoid receptor-dependent and independent manners. A mixture of green tea polyphenols (GTPP) induced TNF- gene expression and TNF-a release from cells.5

ANTIOXIDANTS EXTRACTS FROM NATURAL SOURCES

Many other extracts have been used in studies to demonstrate antioxidative potential. A recent study concluded that the lactoferrin and black tea polyphenols had protective effects against carcinogen activation, DNA damage, cell proliferation, invasion, and angiogenesis in an experimental oral carcinogenesis model9. Phytochemical is found in black raspberries, which are a rich, natural source of vitamins and minerals. Specifically, the active compounds in black raspberries include vitamins A, C, and E, folic acid, calcium, selenium, beta- carotene, ellagic acid, coumaric acid, and quercetin, besides different anthocyanins and phytosterols. Ferulic acid is also a component of raspberries and is active against free radicals such as ROS. Animal studies and in vitro studies suggest that ferulic acid may have direct antitumor activity against breast and liver cancer, and can help in the fight against the effect of carcinogenic compounds like benzopyrene and 4-nitroquinoline 1-oxide. Ferulic acid has pro- apoptotic (programmed cell death) effects that will damage the cancer cells13. The topical combinations of ascorbic acid, vitamin E, and ferulic acid may diminish oxidative stress and prevent the formation of thymine dimmers (damage caused by ultraviolet light) in skin14.

ADVERSE EFFECTS OF ANTIOXIDANTS:

High doses of vitamin A showed to have embryotoxic and teratogenic effects. Large doses of vitamin C (ascorbic acid) may be associated with the inhibition of ovarian steroidogenesis and increased probability of abortion. Antioxidant supplements were once thought to be harmless but increasingly awareness in coming of their interactions and potential toxicity. Also, very little is known about the long-term consequences of mega doses of antioxidants.1 Antioxidant therapy in human reproductive medicine is still a controversy2. Although there are various benefits of fruits and vegetables as they help in reducing the free radical damage from environmental pollutants (including radiation) in observational studies, supplements of Vitamins C and E and beta-carotene generally do not reduce DNA damage from irradiation in many in vitro and animal studies. Reasonable data is available which suggests that Vitamin C has no effect on cancer.4 High doses of Vitamin A showed to have embryo toxic and teratogenic effects. Large doses of Vitamin C may be associated with the inhibition of ovarian steroidogenesis and increased probability of abortion.5 Some studies have shown that, people whose diets are rich in fruits and vegetables have a reduced chance of developing cancer and an increase in the concentration of beta-carotene in their blood. However, supplements of beta-carotene do not have an anticancer effect, and they actually increase cancer in smokers.4

ANTIOXIDANTS IN ORAL HEALTH

An antioxidant is a molecule which inhibits oxidation reaction. Antioxidants terminate the chain reaction caused by free radicals of oxidation reaction, preventing cell damage or death of the cells. Insufficient levels of antioxidants or inhibition of antioxidant enzymes causes oxidative stress and damage or kill the cells.14 Antioxidants are available from different sources, including vitamins, minerals, enzymes and hormones, as well as food and herbal supplements. These supplements may be in bar, gel, capsule, drops and tablet forms. As an alternative medicine, herbal therapy is a treatment modality to remedy many medical and dental conditions. Antioxidants have also been used in combination with dried, fresh, and blended herbal paste.15 The majority of herbal supplements include green tea catechins, aloe vera, star anise oil, calendula extract, ammonium glycyrrhizate (from liquorice root), fennel oil, and neem extracts.16 Most recently, dental manufacturers and distributors have incorporated antioxidant supplements into toothpastes, mouth rinses/mouthwashes, lozenges, fluoride gels and dentifrices, oral sprays, breath fresheners, and other dental products for the control of gingival and periodontal diseases17. Antioxidants taken systemically, such as foods and vitamin supplements, topical antioxidants may have an effect on oral cells. The success of topical antioxidants on skin cells suggests perhaps a similar effectiveness of topical compounds on cells in the oral cavity18. Research studies are currently under way to examine the effectiveness of combinations of antioxidants applied topically to oral cells. Results from clinical studies, though incomplete, are positive19. In addition, published research studies confirmed that antioxidants that work on skin cells also have an effect on oral, gingival, and periodontal cells.20

Antioxidants, their mode of action and location/significance (Table.1)

CONCLUSION

Oral cavity is the mirror to general health as it is interconnected with other systems of the body. The human body has inbuilt defence mechanism against various disease-causing agents. Antioxidants are the first line of defence against these free radicals. Antioxidants like beta-carotene, lycopene, selenium are believed to have a preventive role against various oral diseases. There is overwhelming evidence that oxidative stress occurs in cells as a consequence of normal physiological processes and environmental interactions, and that the complex web of antioxidant defence systems plays a key role in protecting against oxidative damage. It appears that diets low in antioxidant vitamins cannot only increase the risk of developing gum disease but influence its severity as well and that this has implications beyond gum diseases. The knowledge of antioxidants is useful in reducing the incidence of oral cancers at initial stages though non-invasive techniques. A diet high in antioxidants may reduce the risk of many diseases, including heart diseases and certain cancers. Antioxidants scavenge free radicals from the body cells, and prevent or reduce the damage caused by oxidation, recent clinical studies have shown the beneficial effects of these antioxidants in oral leukoplakia, a characteristic oral precancerous lesion. Hence, natural products like fruits and vegetables helps in preventing oral cancers at an early stage. Nutrients will be widely utilized and will play an important role in preventing cancers once their effectiveness is conclusively demonstrated by prospective clinical studies, and when their mechanisms of actions are more clearly understood. Thus, antioxidants play a role in majority fields of dentistry, but there exists confusion in using it in a fully-fledged manner, since clear-cut dosage level and safety level of antioxidants uses have not been clearly stated. Simply if any drug enhances free radical activity, the usage of antioxidants will neutralize this effect. There is lack of protocols for quality control and quality parameters in standardizing antioxidants with respect to potency and safety doses for its usage in patients. The properties of most of the antioxidant have been studied to understand their mechanisms and to clarify their activities. Future researches should continue with the aim of investigating the antioxidants biocompability, pharmacokinetics, pharmodynamics and understanding their pathways on human health. Some antioxidants have more anti-inflammatory activity whereas some have more anti-tumour properties. A well-balanced diet, which includes consuming antioxidants from whole foods, is best. If insisted on taking a supplement, seek supplements that contain all nutrients at the recommended levels.

REFERENCES