In physiological conditions in the body, there is a balance between prooxidants and antioxidants. The free radicals are physiologically produced during cellular metabolism if there is an imbalance or alteration in the antioxidants level which results in a condition called oxidative stress occurs. Oxidative stress represents a widespread phenomenon involved in several pathological conditions. Oxidative stress can lead to cell damage through microdamage to the cell membrane, protein deactivation, DNA damage, and stimulation of cell signaling molecule-induced tissue damage.
Human saliva is a diagnostic fluid that is rich in antioxidant compounds and plays a primary role in the protective mechanism. These antioxidants neutralize the free radicals, including Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS) which releases due to oxidative stress and preventing cell breakdown, tissue damage, and DNA mutations. Whole human saliva may contain numerous antioxidants which are measurable tools to monitor the oxidative processes in the oral cavity and also help in guiding the development of new drugs or treatment plans. This article gives extensive information on salivary antioxidants and their role in various common oral lesions like inflammatory disease, pre-malignant, and malignant diseases, autoimmune diseases, etc.
Saliva is an accessible and acceptable biofluid that contains components derived from the mucosal surfaces, gingival crevices, and major/minor salivary glands. Saliva also contains various chemical substances and microorganisms that colonize in the mouth with other external substances and so can potentially provide an insight into the relationship of the host with the environment. The salivary antioxidant system is one of the key salivary defensive mechanisms and a protective factor for oral mucosa against oral pathogens. There are multiple different antioxidant compounds in human saliva. To maintain the homeostasis of the oral cavity in a healthy person, there is a proper balance between oxidative stress and the antioxidant system. If there is any imbalance occur between these systems which leads to an increase in free radicals’ status and results in disease or disorder. According to the new definition, oxidative stress represents the disturbance of redox-dependent signaling pathways and the processes they control. Oxidative stress is required for a healthy person for normal daily life in the process of ATP generation. This oxidation process is part of the regulatory biochemical function which releases the free radicals and maintain the body equilibrium through the production of antioxidant.
During biological processes, there is the production of these endogenous free radicals that can be attached with each particle, which are highly reactive molecules because of the unpaired electron. These radicals are highly unstable, chemically reactive, and short half-life which is eager to react and capture an electron from other molecules, resulting in irreversible changes in chemical and physical changes of the cell and its component. The cellular components are lipid, carbohydrate, proteins, and nucleic acids which are exposed to the harmful action of free radicals resulting in oxidative damage to the cell/tissue/organ. If there is overexpression of free radicals and under expression of antioxidants, it may lead to pathologies like tumor, mutagenesis, and carcinogenesis. The generation of free radicals is not indicative of a negative impression. Many research workers have conducted studies and associated the function of free radicals in health and diseases. In the physiologic process, the free radical will produce during tissue repair, ATP synthesis, and immune response. 7 The main etiologic causative agents are identified in oral diseases which induce the formation of free radicals are UV radiation, drugs like corticosteroids, anticancer drugs, pesticides, immune disturbance, diet, pollution, dental materials, alcohol, smoking, and stress lifestyle, etc.
To counteract these free radicals, there is a protective mechanism like antioxidant will release for protecting and neutralize the free radical i.e., oxidative status and maintain the health of the individual. If the balance between the oxidative status and antioxidative status is broken, then the natural defense system fails and leads to various diseases and disorders. Antioxidants are also called as free radical scavengers means the molecules capable of inhibiting the oxidation of another molecule. Antioxidants are classified based on the function and based on the function, nature, and action, source. (Table-1) Currently, there is growing interest in the linkage between the role of antioxidants and oral disease because overproduction of reactive oxygen species due to inflammation or by the lack of antioxidants is still unclear.
ROLE OF OXIDATIVE STRESS AND ANTIOXIDANTS IN THE PATHOGENESIS OF THE ORAL DISEASES:
The antioxidant of saliva has gained a primary subject in biomedical research because it has a main key role in the pathogenesis of diseases in the oral cavity. These antioxidants protect the oral cavity from the oxidative stress of free radicals and prevent the pathogenesis of oral diseases. Saliva is considered a mirror of the body in various hormonal, immunological, toxicological, and infectious diseases as biological markers and an excellent tool for monitoring oral and systemic health. These salivary antioxidants level illustrates the oral health as well as systemic health of an individual. Oxidative stress can lead to cell damage through microdamage to the cell membrane, protein deactivation, DNA damage, and stimulation of cell signaling molecule-induced tissue damage. Some molecules are more vulnerable to oxidation (i.e., "electron theft") than others. In particular, some of the molecules in cell walls, containing unsaturated lipids, are particularly susceptible to the attack of free radicals. Other vulnerable molecules include RNA, DNA, and protein enzymes. Oral cells are uniquely susceptible to free radical damage because the mucus membranes allow rapid absorption of substances across their surfaces.15 In oral tissues, infection from gum disease can generate oxidative stress as can alcohol, nicotine, hydrogen peroxide, and other dental procedures and substances such as hydrogen peroxide, dental cement, and composite fillings. The increase in free radicals from oxidative stress leads to further breakdown of cell walls and oral tissue. The free radicals and have been identified as clinically relevant in vascular, inflammatory, and oral diseases.
ROLE OF ANTIOXIDANTS IN DENTAL CARIES:
Dental caries is the most common oral disease affecting all age groups of people. Dental caries is a multifactorial inflammatory disease that is initiated by acid production during carbohydrate fermentation with help of bacteria. This inflammatory response in the tooth due to oxidative stress leads to the destruction of enamel, dentin, pulp, and cementum. The role of oxidative stress in dental caries is still not clear and requires depth research. There are many studies conducted on the relationship between Total Antioxidant Capacity and dental caries of children and adults. Most studies show that TAC levels are significantly higher in the caries active group than in caries-free subjects. There have been a few studies that have shown that a dental caries person has lower TAC levels than a caries‑free person. Few authors suggested that there are alterations in salivary total antioxidant capacity, catalase level was significantly higher in the caries active groups when compared to control groups. Catalase protects cells from hydrogen peroxide generated within aerobic organisms which play a vital role in the acquisition of tolerance to oxidative stress as an adaptive response of cells.
ROLE OF ANTIOXIDANTS IN PERIODONTAL LESION:
In recent years, chronic periodontal disease is the most common inflammatory disease of the oral cavity due to oxidative stress. Periodontal disease is an inflammatory condition that alters the periodontium, resulting in the destruction of supporting structures like an alveolar bone which leads to tooth loss.
The antioxidative role of saliva in the aim of neutralizing free radicals and reducing the oxidative damage of the periodontal tissue cells, which this secretion accomplishes by the presence of enzymatic and non-enzymatic antioxidants. Among them are dominant: salivary peroxidase, superoxide dismutase, glutathione peroxidase, catalase, uric acid, albumin. Saliva is also rich in non-enzymatic antioxidants such as ascorbic acid, albumin, glutathione, lactoferrin, vitamins, and uric acid, which is the main representative agent of this group [30]. These antioxidants protect against the free radicals which damage the biomolecules of cells and promotion of proinflammatory cytokines like such as tumor necrosis factor (TNF)-alpha, interleukins (IL1-beta and 6).
ROLE OF ANTIOXIDANTS IN ORAL CANCER:
Oral leukoplakia is the most common potentially malignant disorder of the oral mucosa. Many cases of oral cancer are preceded by a variety of potentially malignant oral disorders, of which leukoplakia appears to be most common. Volkova et.al conducted a study on leukoplakia patients and concluded that Salivary SOD and total antioxidant capacity were lower in patients than in controls.
Oral cancer also called oral squamous cell carcinoma (OSCC), is one of the second most common types of cancer in the world because of delay in diagnosis and clinical presentation, poor prognosis, lack of specific biomarkers, and expensive treatment. Salivary antioxidants are considered as one of the biomarkers for the identification of oral precancer and cancerous lesions. The role of the Superoxide Dismutase enzyme is considered a tumor suppressor and it was studied in cancer patients. It was observed that SOD is decreased and its expression is used as a biomarker for oral cancer. There is an alteration in glutathione levels in carcinogenesis in which Gamma‑glutamyl transpeptidase is an enzyme that catalyzes the breakdown of glutathione. Hence there is an increase in the level of glutathione in oral cancer compared to controls.
ROLE OF ANTIOXIDANTS IN ORAL SUBMUCOUS FIBROSIS (OSMF):
Oral submucous fibrosis (OSMF) is a precancerous condition that affects the collagen fibre of the connective tissue due to the habit of betel chewing i.e areca nut consumption. The phenolic compounds in areca-nut are responsible for the formation of free radicals among betel-quid chewers. These free radicals are derived from lipid peroxidation which has a role in the initiation and progression of OSMF.
ROLE OF ANTIOXIDANTS IN RECURRENT APHTHOUS ULCER:
Recurrent aphthous stomatitis is the most common ulcerative disorder of the oral mucosa, which is characterized by painful, single, or multiple, round shallow ulcers covered by yellowish-greyish pseudomembranous with well-demarcated erythematous margin.
ROLE OF ANTIOXIDANTS IN AUTOIMMUNE DISEASES:
Several researchers have shown that the imbalance between free radicals and reactive oxygen species plays a major role in the initiation and progression of oral autoimmune inflammatory lesions. Lichen planus is a common autoimmune disease among the middle age groups of people. There was an evaluation of oxidative stress in lichen planus on antioxidants level and it was shown that an increase in the levels of SOD, with decreased catalase, glutathione peroxidase levels than controls. Systemic lupus erythematosus (SLE) is an autoimmune chronic inflammatory disease. The etiopathogenesis of SLE suggested that free radical and oxidative stress may play an important role. There is an increase of Reactive Oxygen Species (ROS) or impaired antioxidant protective systems that are responsible for the oxidative stress in SLE.
ROLE OF ANTIOXIDANTS IN HIV INFECTION:
There is an alteration in glutathione levels in HIV‑infected patients due to oxidative stress, thus glutathione supplements were prescribed for their survival. Therefore, glutathione is considered a tool marker to identify the transformation of HIV‑infected patients into AIDS patients. There are salivary total antioxidant levels were significantly lower in HIV-positive patients compared to healthy controls
ADVANTAGES OF ANTIOXIDANTS IN DENTISTRY:
- Antioxidant and oxidative stress markers will guide us the different stages or grades of tumor
- The changes in antioxidant balance in connection with an important link of the pathological process in the oral cavity, so that these antioxidants could be used as potential diagnostic tool markers for providing an adequate method of treatment for improvement of dental status.
- The changes in the salivary antioxidant enzymes suggest that saliva may be an appropriate marker for the prognosis of oral diseases compared with the conventional invasive serum antioxidant enzyme.
CONCLUSION:
The whole saliva contains antioxidant in enzyme and non-enzymatic compound which is simply measured indicators of oxidative processes. Oxidative stress that results in damage of cells and their components is the basic pathway of physiologic processes and pathologic diseases. Since saliva is a non-invasive technique to determine the salivary concentrations of antioxidants allows the evaluation of the oxidative stress and defensive capacity of the oral mucosa, and in this way, we can prevent many pathological conditions in the oral cavity. This may provide a hallmark tool for the diagnosing, development, and monitoring of new treatment strategies for oral diseases as well as systemic diseases.