Role of Antioxid Ants as an Adjunct in Periodontal Therapy

INTRODUCTION

Periodontal disease is an inflammatory disorder that leads to tissue damage and bone loss as a result of complex interactions between pathogenic bacteria and the host‟s immune response. The majority of periodontal treatment modalities attempt to arrest the progression of periodontal destruction in order to avoid tooth loss. But there are some situations when periodontal therapy is not effective despite the provision of proper treatment. Therefore, periodontal research should attempt to identify background factors that may explain the response to therapy. Systemic factors such as a balanced nutrition or nutritional supplementation have not been thoroughly evaluated in periodontal research, although reports of the possible effects of nutrient deficiency and supplementation have appeared early in the periodontal literature.^1-4

ROLE OF ANTIOXIDANTS

Antioxidant levels is as important as knowing your cholesterol levels, or your blood pressure. There are many studies linking free radical damage at the cellular level not only to premature aging, but also to virtually everything that ails us including periodontal disease. Free radicals are molecules or atoms that have lost an electron whichcauses them to become unstable and highly reactive. Antioxidants are the nutrients in fruits and vegetables that can neutralize free radicals by donating an electron without becoming unstable themselves. Unfortunately, because of depleted farm soils and early harvesting of crops to facilitate distribution to market, the fruits and vegetables that we find available to us today have significantly lower nutrient content then even 10 years ago and dramatically lower nutrient content from 50 years ago.

If your diet lacks certain nutrients, it may be more difficult for tissues in your mouth to resist infection. This may contribute to

periodontal disease, a major cause of tooth loss in adults. Although poor nutrition does not cause periodontal disease directly, many researchers believe that the disease progresses faster and may be more severe in people with nutrient-poor diets because of compromised host response. Chronic subclinical inflammation is the driver of most, if not all, chronic diseases. It is a fact that the same basic inflammatory state underlies heart disease, cancer, Parkinson‟s disease, Alzheimer‟s disease, osteoporosis, osteoarthritis, chronic pain, and periodontitis^(5-8) . The manifestation of the chronic inflammatory state is likely to differ depending on ourgenetic disposition to disease expression. The term Genetic Polymorphism is used to describe the individual differences in our genes that can lead to the expression of various diseases

MECHANISM OF ACTION OF ANTIOXIDANTS

Antioxidants may be regarded as those substances which when present even at low concentrations with those of an oxidisable substrate will signifi cantly delayor inhibit oxidation of that substrate. Free radicals which are harmful usually arise during metabolism and sometimes the immune system cells create them to neutralise harmful pathogens. Environmental factors like pollution, radiation and smoking may spawn free radicals. Antioxidants neutralise free radicals by donating one of their electrons, ending the electron stealing reaction. The antioxidant nutrient, however, does not become a free radical by donating an electron because they are stable in either form. Important antioxidants include:

1. The chain breaking or scavenging ones like vitamin E (alpha tocopherol), vitamin C (ascorbic acid), vitamin A (beta carotene), urate and bilirubin;
2. Those substances containing thiol groups - the ‘preventative antioxidants’, that function largely by sequestering transition metal ions and preventing Fenton reactions and are therefore largely proteins by nature (eg albumin, transferrin, lactoferrin, caeruloplasmin, haptoglobin, and ascorbic acid); and
3. Enzyme antioxidants that are enzyme systems that function by catalysing the oxidation of other molecules (eg catalase and glutathione peroxidase). The equilibrium between antioxidant defence, repair systems and pro-oxidant mechanisms of cell damage may be tipped in favour of tissue destruction by increase in radical production or by a lowered antioxidant defence.^2,9

In the early onset of periodontitis, polymorphonuclear leukocytes are functionally activated and exhibit increased free radical production. There is a delicate balance between the infl ammatory- immune cell hypofunction and hyperfunction which are maintained by enzyme based mechanisms (which are activated following degranulation) and oxygen dependent pathways (produces free radicals species).⁹ ROS cause tissue damage through numerous ways that include DNA damage (base hydroxylation and lipooxygenase); protein damage(gingival hyaluronic acid and proteoglycans); lipid peroxidation and stimulation of proinfl ammatory cytokines.¹⁰ The antioxidant micronutrients are important not only for limiting oxidative and tissue damage, but also in preventing increased cytokine production, which is a result of prolonged activation of the immune response. Dietary and other enzymatic antioxidants protect the lipids of lipoproteins and other biomembranes against oxidative damage by intercepting oxidants before they can attack the tissues. It is important to have an adequate antioxidant intake from both diet and supplementation if needed, and can be a valuable adjunct in the treatment of chronic inflammatory dental disorders.¹¹

ANTIO XIDANTS IN PERIODONTAL HEALTH

Oral biologists from University at Buffalo’s School of Dental Medicine have shown for the first time that a diet low in antioxidant vitamins can increase the risk of developing gum disease. The research was conducted in the University of Buffalo’s Periodontal Disease Research Center, They evaluated the examined serum levels of antioxidant nutrients and their relationship to periodontal disease, using datafrom 9,862 subjects between the ages of 20 and 90 who participated in study. To establish an antioxidant profile, researchers assessedlevels of vitamins A, C and E; selenium; a-carotene; b-cryptoxanthin; lycopene; and lutein. Periodontal-disease status was established by combining mean periodontal-attachment level, plus the number and locations of detachments. The lowest and highest periodontal disease groups then were compared with antioxidant status. Results showed that selenium has the strongest association with gum disease, with low levels increasing the risk by 13-fold. Low levels of vitamins A and C, acarotene, and b-crytoxanthin also increased the risk of gum disease significantly.low levels of most antioxidants are a risk factor for periodontal disease and infection. Free radicals are released as a result of bacteria clearance and killing. Periodontal tissue depends on natural antioxidants to overcome this oxidative stress and maintain homeostasis. When antioxidants are depleted, the ability of gum tissue to overcome oxidative stress, maintain normal tissue and control the bacterial damage appears to be compromised.”⁽⁹⁾

Battino et al. state that in gingivitis, the inflammatory infiltration consists mainly of lymphocytes, plasma cells and neutrophils. While vitamin E dramatically decreases, CoQ¹⁰ remains unchanged despite the increased amount of cells present in the periodontally affected tissues, indicating that the continuous oxidative stress which occurs in these structures affects the antioxidant pattern of the tissue. ⁽¹⁰⁾ Changes in the gingival microenvironment could impair apoptosis (programmed cell death) and promote enhanced release of reactive oxidative species (ROS) by phagocytes; decreased catalase (CAT) and superoxide dismutase (SOD) activity could promote accumulation of ROS and result in additional tissue destruction.⁽¹¹⁾

Krol s study of total antioxidant status in peripheral and gingival serum correlated with periodontal clinical status showing significantly lower total antioxidant status in venous blood serum in each subgroup as compared with controls. He concluded that oxidative stress in periodontitis expressed by elevated concentrations of ROS and accompanied by suppressed antioxidant activity in gingival

gingival blood may accelerate lesion formation in periodontal tissues.⁽¹²⁾. Further evidence for a role for ROS in tissue destruction with inflammatory periodontal disease was discussed by Waddington et al. Polymorphonuclear leukocytes (PMN’s) during an inflammatory response and are regarded as being highly destructive in nature. This is evidenced by ROS oxidation products, elevation of iron and copper ions (catalyzing the production of the most reactive radical species) and the identification of an imbalance in theoxidant/antioxidant activity within periodontal pockets, as well as the identification and characterization of connective tissue metabolites in gingival crevicular fluid (GCF) resulting from the degradation of periodontal tissues, notably alveolar bone.⁽¹³⁾

MICRONUTRIENT INTERACTIONS

Increased production of reactive oxidative species (ROS) necessitates an elevated need for zinc, copper and selenium, nutrients which are involved in antioxidant defenses. Systemic glutathione (GSH) is decreased with inflammation. The functions of GSH include antioxidant defense and immune regulation.⁽¹⁴⁾ The vitamins pyridoxal phosphate (B6) and riboflavin (B2) are important in maintaining GSH status.⁽¹⁵⁾ Selenium has important oxidation-reduction functions, and selenium-dependent GSH enzymes are involved in changing lipid and phospholipids hydroperoxides to harmless products⁽¹⁶⁾, neutralizingthe inflammatory process at the cellular level. Therefore vitamins B2, B6, copper, zinc and selenium are needed to maintain systemicglutathione and selenium-dependent GSH enzymes for antioxidant defense, immune regulation, and neutralization of the inflammation process at the cellular level. Micronutrients—beta-carotene andvitamins A, C and E—can be depleted during inflammation.⁽¹⁷⁾ As mitochondria (the power house of the cell) produce energy, theyrelease ROS within the cell. In a study in Sagan et al suggested that dietary vitamin C enters the mitochondria and protects against oxidative injury.⁽¹⁸⁾ These vitamins support immune functions and are involved in the maintenance of structural and functional integrity of epithelial tissues and physiological or metabolic parameters relevant to periodontal health.⁽⁸⁾

Lester Packer states vitamins C, E, CoQ10 (ubiquinone), alpha-lipoic acid, and selenium all function as part of an antioxidant network. When they neutralize a free radical they become a weak freeradical themselves. But they function collectively and have the ability to recharge each other. Carotenoid antioxidants on the other hand are free radical traps and cannot be recharged. They are the first line of defense and have a protective effect on vitamins C and E. When the carotenoid levels are diminished, the rest of the antioxidant network begins to unravel.⁽¹⁹⁾ . Svilaas et al demonstrated that carotenoids are predictors of overall antioxidant status.⁽²⁰⁾

Enwonwo reports that deficiencies of several essential macro- and micronutrients adversely influence the prognosis of periodontal infections.⁽²¹⁾ later he adds that good dietary practices and optimal nutritional status are important in mitigating the severity of inflammatory periodontal lesions but are likely of limited value if the stimuli from dental plaque are not removed.⁽²²⁾

Periodontal diseases are associated with an imbalance between oxidants and antioxidants in favor of the former due to both an increase in free radical production and a defect in the total antioxidant activity of saliva.⁽²³⁾ It is interesting to note that the concentration of antioxidants in saliva does not appear to mirror those of plasma. Sculley et al stated that the influence of nutrition on antioxidant status may lead to a possible nutritional strategy for the treatment of periodontal disease.⁽²⁴⁾ later they state that periodontal disease isassociated with reduced salivary antioxidant status and increased oxidative damage within the oral cavity.⁽²⁵⁾

Inter relationship of Periodontal and Systemic Conditions

Periodontal diseases may have wide spread systemic effects. While these effects may be limited in some individuals, periodontal infections may significantly impact systemic health in others and may serve as risk indicators for certain systemic diseases or conditions. Figuero et al noted that the catabolic effects of nicotine could be reversed by the addition of antioxidants such as CoQ or Pycnogenol and phytoestrogens.⁽²⁶⁾ With regard to diabetes, advanced glycation endproducts (AGEs) present in diabetic gingiva may be associated with a state of enhanced oxidative stress, a potential mechanism for accelerated tissue injury⁽²⁷⁾ which we so frequently observe clinically. This implies that the diabetic has an even greater requirement for antioxidants.

Serum and gingival crevicular fluid (GCF) total antioxidant capacity and superoxide dismutase (SOD) concentrations were significantly lower in menopausal women and chronic periodontitis (p<0.05). A decrease in systemic and local antioxidant defense was observed owning to both menopause and periodontitis. These low antioxidant values in the postmenopausal subjects with chronic periodontitis group suggest that menopause may be a risk factor for periodontitis.⁽²⁸⁾

Conclusion

Recommendation for the periodontal therapy

1. Control bacteria with improved oral hygiene, remove irritants with scaling and root planning
2. Strengthen the host defense response with appropriate supplementation and track baseline and subsequent antioxidant status using non-invasive measurement of skin carotenoids.

surgical objectives like soft tissue regeneration , pocket reduction, bone regeneration, periodontal plastic surgery procedures.

Antioxidant levels appear to be a significant factor in weakening or bolstering host resistance to periodontal disease. In fact, they may just be the missing link. And considering the emerging body of evidence tying periodontal disease to other serious health problems.