Antioxidant and dentistry
Govind Rajpala, Lokesh Patnib, Arasana Dhariwala, Ankit Kumara, Sandeep Visvarmac, Aadesh Kumard
aDepartment of Pharmaceutical Sciences, Sir J.C. Bose Technical Campus, Nainital, Uttarakhand, India
bShree Dev Dental Clinic, Nainital, Uttarakhand, India
cDeep Dental Clinic, Nainital, Uttarakhand, India
dDepartment of Pharmaceutical Sciences, Kumaun University, Campus Bhimtal, Bhimtal, Uttarakhand, India
5.5.1 Introduction
One of the major and leading concerns about molecules available in natural sources are antioxidants. These molecules are useful for reducing as well as preventing the oxidation of some alternative molecules. When oxidation occurs free radicals are produced, these complimentary radicals are free to bind with another molecule and they cause detrimental series reactions that cause cell injury or cell death. This was observed that these molecules are responsible for the oxidation of low-density lipoprotein (LDL) in cardiovascular diseases (CVS) and carcinogenesis. Ageing is one of the factors that occur due to free radicals release. Health-related problems also occur when low levels of antioxidants are taken with diet they may be gout, osteoporosis, skin problems, hair loss, and obesity. Free radicals are neutralized by the antioxidants as they donate their free electrons and helps in chain termination which ends the electron taking reaction (Bhuvaneswari, 2014; Cadenas, 1989).
Free radicals are known to be chemical ions or active ions that hold some charge which is generated due to surplus or inferior count of electrons. They are categorized into two types according to their species; one is a potent reactive chemical known as reactive oxygen species (ROS) and the other one is the group of nitric oxide derivative compound (Cadenas, 1989). Oxygen-free radicals damage the biological mechanism is known as ROS. X-rays, γ-rays, and UV light irradiation may produce damaging free radicals. Free radicals are produced and remain dispersed in the atmosphere as pollutants after the catalyzation of metals. Macrophages and neutrophils also produce free radicals during the Inflammation cycle in the human body. Free radicals also developed in the process of energy generation, when mitochondrial cells utilize oxygen (O2) to create power in the form of adenosine triphosphate (ATP) molecule (Valko et al., 2004; Tiwari, 2004). The oxidative stress would be increased by an inequality in connecting the free radical management and antioxidant count to rummage ROS (Shivana and Gupta, 2013). Based on lipophilic and hydrophilic nature antioxidant can be divided into two subcategories.
- Hydrophilic antioxidants: These are responsible for reaction with oxidants in blood plasma.
- Lipophilic antioxidants: These types of antioxidants help to preserve cell laminate through lipid catabolism.
There are various types of antioxidants available within nature, which could be in the form of enzymes, vitamin, and phytochemicals. Green algae, plants, and fresh leafy veggies are a great source of antioxidants, plants developed antioxidants with the help of UV light present in Sun exposure (Bhuvaneswari, 2014). Attack of free radicals on the human body could be prohibited with the help of antioxidants by creating an extremely composite antioxidant complex that may be enzymic or nonenzymic. Antioxidants work harmonious and in sequence with one to prohibit the oxidation of cells as well as organs (Shivana and Gupta, 2013).
Based on occurrence antioxidants can be classified as:
Exogenous antioxidants are such type of antioxidants which we grab from our diet and supplements that enriched with antioxidant (e.g., retinol, ascorbic acid, and tocopherols). It seems impractical to grab enough antioxidants from our daily diet and food habits to compensate for the daily scavenge of free radicals automatically. So there is the necessity to complete the requirement with a supplement. Supplementation could be of dosage form like capsule, liquid, or tablet that meet the need of exogenous antioxidants. In dentistry, the source of antioxidants may be the kinds of toothpaste, mouth bathe, or oral sprinkler that containing antioxidant additives. The majority of oral additives include green tea, propolis from beehives, dried grape seed, and extract of pine bark (Bhuvaneswari, 2014).
Endogenous antioxidants are those which are produced by our body. Internal antioxidants are responsible for the repair of all damage occurred by the free radical while commencing cell reclamation from the innards on away, instead of it exogenous antioxidants helps only in overhaul a few of the free radical destruction from the surface by challenging (not initiating) cell reconstruction. Examples of five highly dominant internal antioxidants include glutathione (gamma-glutamylcysteinylglycine, GSH receive from yeast and animal tissue extract), alpha lipoic acid (gain from yeast, liver, kidney, and spinach), superoxide dismutase (gain from melon), catalase (present in living tissue), and coenzyme Q10 (CoQ10) (Bhuvaneswari, 2014).
5.5.2 Enzymes as antioxidant
Different enzymes are synthesized inside the human body and work by scavenging free radicals inside the body. These enzymes are superoxide dismutase (SOD), glutathione peroxidase, glutathione reductase, and catalases. Those are the good sample of antioxidants that drop in from the protein and minerals present in our daily food intake. Generally, enzymes required some co-factors to produce maximum antioxidant activity. These co-factors are iron, copper, selenium, magnesium, and zinc (Valko et al., 2004).
- 1. Superoxide dismutase: SOD plays a decisive aspect in the scavenging of ROS. It abolishes anions of superoxide that comes from extracellular origin (Tosun et al., 2019). Superoxide dismutase is the association of stimulant or enzymes that facilitate cellular protection form the ROS by converting free radicals to oxygen (O2) and hydrogen peroxide (H2O2) molecule. Extensive research on SOD conclude that therapeutically SOD is used as anti-inflammatory, anticarcinoma, and protection from radiation (Wang and Zhang, 2015).
- 2. Glutathione peroxidase: Glutathione is a tri-peptide molecule containing cystine, glycine, and glutamic acid, developed inside the body by cellular metabolism. It helps in biotransformation of xenobiotics materials, and protect human body from oxidation and reducing agent. Glutathione transferase enzymes family helps by scavenging of electrophile from the body, which is responsible for cellular deterioration and mutations (Gad, 2014).
- 3. Glutathione reductase: The role in preserving the cellular capacity of antioxidants is Glutathione reductase (GR) (Cardoso et al., 2008). The supply of reduced glutathione is maintained by glutathione reductase; in most cells, one of the most abundant thiol reducers. Glutathione plays an essential character by reducing the count of ROS cells. Species of reactive oxygen act as intracellular and extracellular signaling agents, and complicated chat between ROS heights, glutathione, and other thiols oxidized and levels are decreased also providing the most suited redox control conditions within the cell or the activation of programmed cell deaths by antioxidant enzymes such as glutathione reductase (Couto et al., 2016).
- 4. Catalases: One of the most significant enzymes of antioxidants is the catalase. When hydrogen peroxide is broken down into harmless products like water and oxygen. Catalase is employed as a treatment for several stress-related oxidative illnesses. It is still difficult to implement the catalase enzyme in acceptable concentrations at the suitable place. Nanoparticles for the delivery of catalase to human neural cells and protection against oxidative stress were assessed with these catalase-loaded nanoparticles (Nandi et al., 2019).
5.5.3 Antioxidants and dental caries (antioxidants have a more preventive than a curative effect on following oral problems)
The creation of cavities in the teeth is one of the most common oral conditions. Dental cavities are developed because of lack of available antioxidant, free radical generation, and ROS in saliva (Battino et al., 2002). Uric acid, glutathione, ascorbic acid, albumin, and antioxidant enzymes such as salivary peroxidase are the main antioxidants. Salivary peroxidase system, salivary antioxidant systems, and salivary peroxidase catalyze the peroxidation of thiocyanate ion (–SCN) to generate oxidation products (more stable OSCN–); to suppresses the growth and metabolism, hence inhibiting caries, of several microorganisms. The uric acid constitutes 70% of the total antioxidant potential of the salivary antioxidant system (Cadenas, 1989; Shivana and Gupta, 2013).
Sources of free radical insult in dental therapy (Chapple et al., 2007).
In dentistry, many commonly used dental materials may form free radicals like.
- 1. Materials used as bleaching agents.
- 2. Some components of composite fillings.
- 3. Materials associated with dental cements.
- 4. Materials used for ceramic restoration.
- 5. Metals used in restoration of tooth.
- 6. Tooth implants.
- 7. Drugs used for intracanal medicament.
There are various disorders in the oral cavity which have more preventive than therapeutic effects when studying antioxidants.
5.5.4 Periodontology
The inflammatory response between the bacterial infection and the inflame reaction of the host is periodontal disorders. The main cause of inflammatory response is freely available radicals and ROS. ROS overproduction is evaluated by periodontal pathogens, leading to collagen and periodontal tissue collapse. Collagen breakdown by scavenging ROS generation reverses with the help of antioxidants. Support for antioxidants against periodontal diseases is favored. Ascorbic acid insufficiency is one of the conditions causing gingivitis (Cadenas, 1989; Valko et al., 2004).
Free radical chain response can be damaged by plant oil and green leafy vegetables. Thus, periodontal inflammation can be reduced by these natural sources. Flavonoids from natural sources acquiring antioxidants and anti-inflammatory characteristics, which reduce inflammatory molecule remark in immune system fighters. For example, monocytes found in the gingival connective tissues. In addition to this, the fraction of the cranberry can prevent the production of biofilm by the main pathogen of chronic periodontitis called Phorphyromonas gingivalis. Vitamin E, enriched with the capacity that reduce periodontitis oxidative damage.
Many researchers believe that poor nutrition is more rapid and serious in population with poor nutritional diets. The compromised host response not only because of periodontal disease but also characterized by poor nutrition (Dahiya et al., 2013; Abebe, 2003).
The risk of gum disease is considerably enhanced by low intake of vitamins A, C, β-carotene, and β-cryptoxanthin as well. Low antioxidant content is a risk factor for periodontal and infectious diseases. As a result of bacterial clearance and death, free radicals are released. Periodontal tissue is dependent upon endogenous antioxidants to counteract this oxidative damage and to maintain hemostasis. Inflammation decreases the systemic glutathione (GSH). GSH has antioxidant protection and immunological modulation. Pyridox (vitamin B6) and riboflavin (vitamin B2) are playing vital role in preserving GSH position. Selenium has significant oxidation and selenium dependent GSH enzymes are responsible for changes in the hydroperoxides in lipids and phospholipids to harmless products, thus neutralizing the inflammatory process at cell levels. Therefore, systemic glutathione and selenium-dependent GSH enzymes for antioxidant defense, immunological regulations, and cellular neutralization of the inflammation process are required for the maintenance of vitamins B2, B6, copper, zinc, and selenium. Micronutrients—beta-carotene and vitamins A, C, and E during inflammation may be decreased. As mitochondria (cell’s power house) generate energy, responsible for ROS to release inside the cell (Labrecque et al., 2006; Moskaug et al., 2005; Nakamoto et al., 1984).
5.5.5 Clinical studies
The present study shows that the supplementation of oral lycopene and green tea extract is good for salivary uric acid and plays an essential role in gingivitis treatment. While the study focused gingivitis, the results of which can be assessed within 4–6 weeks, to authorize the performance of antioxidant remedy in periodontal disorders, further longitudinal research with bigger sample size paired with other inflammatory markers are necessary. Research into the treatment of gingivitis and periodontitis should be focused on and nutritionally supplemented with exogenous antioxidants (Nakamoto et al., 1984).
5.5.5.1 Restorative dentistry
Restorative dentistry implies how missing or damaged teeth are substituted and future dental disorders are prevented. Comparative restoration alternatives include fillings, crowns, bridges, and implants. Epigallocatechin-3-gallate molecule of green tea had a spinal effect on the avoidance of caries (Carnelio et al., 2008). Antibacterial activity was shown by Cranberries against Streptococcus mutans and to stop tooth decay, especially by their oligomers of type A. Pine bark and grape extracts have been useful in restoring caries and increasing bond strength. In particular to increase lower bond strength values after bleaching for restorative therapies (Schmidt et al., 2003; Berger et al., 2013).
5.5.5.2 Orthodontics
Orthodontics is the dental branch that corrected teeth and jaws that were wrongly positioned. Crooked teeth that do not fit properly together are more difficult to keep clean, risk loss early because of dental decay and periodontal disease and cause more stress on jaw muscles. Similar agents can be used in orthodontics to boost bracket strength. Ascorbic acid solutions were employed in bracket binding to boost bond strength values. In bone development, antioxidants also play an important role. Altan et al. revealed the systemic application of propolis at the suture area accelerates the creation of bones. In a recent study, pine bark extract solution was used instead of ascorbic acid solution (Vidhya et al., 2011).
5.5.5.3 Oral–maxillofacial surgery
Oral and maxillofacial surgery includes a wide variety of facial and skeletal diseases treatment, including jaws and oral caries. Common oral operative difficulties (e.g., teeth affected, dental implants), disorder on the jaw and congenital facial, facial trauma, mouth cancer, gland salivary illness, temporomandibular joint disorders, and several benign diseases (e.g., jaw tumor and cysts) (Aksakalli et al., 2013).
According to Ohnishi et al., the alveolary loss of the bone, accompanied by decreased expression of endothelial nitric oxide synthase in the mice, is due to reactive oxygen, for which hydrogen peroxide, and the production of oxidative stress is an underpinning systemic condition to enhance alveolar bone loss. Peri-implantitis caused by gram-negative, anaerobic bacteria which accumulate in subgingival areas. Supplements of antioxidants are used to treat peri-implantitis. Sheresta et al. stated that extract of grape seed has a beneficial effect on peri-implantitis treatment. For bone healing and bone creation, it was revealed that a compound found in propolis was caffeic acid phenethyl ester which considerably improved bone healing in rat models (Maxwell, 1995; Ohnishi et al., 2009).
5.5.5.4 Oral cancer
In several phases of oral carcinogenesis, antioxidants have preventative and therapeutic potential. Recently, researchers have claimed that oral cancer morphologies are inhibited after taking antioxidants. The proanthocyanidin administrations present in flavonoid structures have the ability to inhibit cell development and oral cancer proliferation. Dietary antioxidants help to prevent oxidative damage in lipids and other membrane molecules by removing oxidants before they try to destroy cells (Shrestha et al., 2012).
Antioxidants act as chemopreventive agents of cancer by reversing premalignant lesions such as oral leukoplakia reducing oral carcinogenesis. The pathogenesis of cancer which can come out of poor dietary habits and lifestyles has been identified as having an influence on oxidative damage. This process can result in DNA damage, a fundamental mechanism for the formation of cancer. The free radical defense requires adequate antioxidant state (Garewal, 1995).
The diet must be adapted to lower the hazard of oral and pharyngeal cancer, in particular oral cell carcinoma, principally to limit calorie intake through monosaturated fat and red meat. Dietary micronutrients such as vitamin A, β-carotene, lycopene, ascorbic acid, alpha-tocopherol, zinc, and selenium are antioxidant in nature should be included in food habits (Carvalho Rde et al., 2013; King et al., 2007).
The use of antioxidant nutrients inhibits cancer cell development and kills them with apoptosis (programmed cell death), stimulates cytotoxic cytokines, expression of genes, and prevents the blood supply to the tumor formation or cellular differentiation (Shirataki et al., 2000; Skibsted et al., 2006).
Retinoids are the natural and synthetic derivatives of vitamin A, emanate in the body from retinyl esters, carotenoids, and retinal obtained from diets. Retinoid receptors (RARs) and retinoid X receptors (RXRs) modulate the actions of retinoids. There are three subtypes of retinoids designated as α, β; both RARs and RXRs have been described (San Miguel et al., 2011; Baudet et al., 1991).
The lack of these dietary vitamins, systemic or mucous levels will interact with tobacco and raise the chance of precancerous mouth lesions. It would be worth continuing research of novel synthetic medicinal products for the regulation of RAs and independent receptors. It seems that the use of oral squamous cell carcinoma apoptotic potential would result in contemporary therapy; which may be less hazardous to normal cells because of their disciplined pathways of physiological survival (Swapna et al., 2014).
It is suggested that these new treatments might also treat epithelial dysplasia effectively. Ideally, chemoprevention is the basis of cancer control. A number of dietary components and micronutrients have a great potential for induction of apoptosis with the addition of the chemical therapy and chemopreventive medicines. These agents include green tea (EGCG and other) components (e.g., carotenoids (lycopene), retinoids, and many more phytochemicals). β-Carotene is a precursor of vitamin A, generally found in dark green leafy vegetables like spinach orange or yellowish vegetables like mango, carrots, oranges, papaya, and sweet potato (Shafer et al., 1993; Battino et al., 2002).
Lycopene is a major serum carotenoid, a red pigment antioxidant. This pigment contains fat-soluble red in some fruit and vegetables. Apricots, tomatoes, papaya, and other yellow fruits are the principal sources of lycopene. Lycopene and other foodstuffs rich in carotenoids are also inversely linked to neoplasms of the higher digestive tract, including mouth cancer. The protection of essential cellular biomolecules including lipids, lipoproteins, proteins, and DNA has suggested that lycopenes inhibit carcinogenesis and atherogenesis. Lycopene has the unusual characteristic to link with chemical species reacting to oxygen, therefore this is the most effective biological antioxidant (Gopinath, 2006; Hsu et al., 2003; Devasagayam et al., 2004).
5.5.6 Oral submucous fibrosis
Oral submucous fibrosis (OSF) is a well-known oral precancer disease, found mainly in South Asian ethnic populations orally (Sankaranarayanan et al., 1997).
It is characterized by a distinctive global fibrosis of oral submucosal soft tissues which results in a strong oral mucosa, which leads to gradual failure of the mouth, rigidity of the lips, and difficulties in lifting the tongue. An estimated prevalence of 0.2–1.2% in India is estimated in Oral submucus fibrosis (OSF) (Rao and Agarwal, 2000; Fig. 5.5.1) connected with the chewing of betel nut products. In India, OSF prevalence varies from 0.2% to 1.2%.
It is a chronically progressive oral cavity and oropharynx scar disease, characterized by an epithelial atrophy and an inflammatory juxta-epithelial reaction with progressive lamina propria and deeper connective tissue fibrosis. The steepness of the mouth causes a gradual decrease in the opening of the mouth (Rao and Agarwal, 2000).
5.5.7 Repeal of oral leukoplakia with antioxidants
The reversal or relapse of premalignant abrasion like leukoplakia is an essential step to prevent cancer. Any agent selected for testing in premalignant lesions whose final objective is to seek the prevention of cancer should be minimized or preferable to no toxic because the intervention will expose many subjects whose sore are rare to evolution to cancer. In developing agents for general population use to reduce oral cancer incidences, antioxidants like β-carotene and vitamin E are preferred. Intervention tests on chewers of quid-tobacco and betel reveal that vitamin A delivery causes total recovery of leukoplakia (Millen et al., 2004; Fig. 5.5.2). The synthetic retinol most widely employed, 13 cis-retinoic acid is hazardous even in extremely low-dose applications. The usage of comparatively nontoxic antioxidants like beta-carotene and vitamin E is becoming increasingly important.
A study evaluating the effect of lycopene on oral cancer showed that high dosages of lycopene (8 mg/day) are good for oral health improvements (Reddy, 2011).
In several phases of oral carcinogenesis, antioxidants have preventative and therapeutic potential.
Researchers recently shown that oral cancer characteristics are inhibited with the ingestion of antioxidants. Proanthocyanidin administrations in antioxidant flavonoid structures have a capacity to lower cell development and proliferate oral carcinomas. Dietary antioxidants can prevent oxidative damage to the lipids and other membrane components by intercepting oxidants before attempting to degrade tissues (Couto et al., 2016).
Conclusion
With the help of this chapter it may concluded that free radical poorly associated the dentistry and causes serious oral health issues but antioxidants present in different plants and other resources terminate the free radical that rectify the oral health issue caused by it and also act as preventer for free radicals by regular use of antioxidant in food habits. Oral intake of extracts of lycopene and green tea, supplementation is directly associated with salivary uric acid levels and perform an essential role in the execution of gingivitis. This study may help to overcome the oral problems by using antioxidants in routine diet.
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