Oxidative Stress and Antioxidants in Oral Health

Introduction

The human oral cavity is constantly subjected to a dynamic environment subject to food, bacteria and oxygen in complex biochemical reactions. Though oxygen is required in the normal metabolic processes, it is also the cause of the development of reactive oxygen species (ROS)- highly reactive molecules in the form of free radicals. When the radicals overwhelm the antioxidant defense of a body, oxidative stress is experienced.

Oxidative stress has become an important concept in the pathogenesis and pathophysiology of periodontitis, oral mucosal lesions, and oral cancer in the context of oral health. Oxidative damage is highly susceptible to the oral tissues due to the rich vascularization and cellular activity of the tissues.

Luckily, the human body has endogenous antioxidants (those produced inside the body) and exogenous antioxidants (those acquired in the diet and oral hygiene products) that counter these free radicals. The molecular aspects of the actions of oxidative stress and antioxidants can be used to better prevent and treat oral diseases.

Learning steroid biochemistry: Oxidative Stress

Free Radicals and Reactive Oxygen Species (ROS)

Free radicals are erratic compounds that have an electron with no partner. The ROS created in the oral cavity include superoxide anions (O 2, -), hydrogen peroxide (H 2 O 2), and hydroxyl radicals (OH) in the normal cells in respiration and inflammation.

In normal states, ROS have positive effects on cell signaling, host defense and wound healing. Excessive generation of ROS however, as a result of environmental stress, inadequate oral hygiene, smoking or infection overwhelms the antioxidant defense system, resulting in oxidative stress.

Oxidative Stress in the Oral Cavity

Oxidative stress causes damage to vital biomolecules such as lipids, proteins and DNA. This damage may be in oral tissues as:

• Lipid peroxidation: Cell membrane disintegration, tissue inflammation and necrosis.
• Protein oxidation: Disturbance in cellular structural and enzymatic activity of cellular proteins.
• DNA damage: Mutations and defects in cell replication which could cause carcinogenesis.

The mouth cavity is susceptible to oxidative imbalance by its exposure to external stimuli (such as tobacco smoke or alcohol) and pathogens.

Vitality of Oxidative Stress in Oral Diseases

Periodontitis

Periodontitis can be described as a chronic inflammatory condition that affects the tissues that hold the tooth. It starts off as gingivitis and may cause severe bone and tissue loss in case it is not controlled.

Its development is highly dependent on oxidative stress. ROS are formed by the immune cells like neutrophils and macrophages during bacterial infection to destroy invading bacteria. But during the period of over release of ROS, it will cause destruction of the own periodontal tissues of the host.

It has been found that periodontitis patients contain increased malondialdehyde (MDA) – an indicator of lipid peroxidation, and reduced the activity of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPx). This disequilibrium is a factor that leads to the degradation of tissues and alveolar bone loss.

Oral Cancer

Oral squamous cell carcinoma (OSCC) represents the commonest type of oral cancer. Chronic oxidative stress is identified to induce carcinogenesis in a number of molecular pathways:

• Unstable DNA mutation and genome by damage through ROS.
• Oncogenes are activated, and the tumor suppressor genes are inhibited.
• Chronic inflammation, which creates a positive microenvironment in accordance with tumor development.

Smokes of tobacco, betel nut chewing, and alcohol, which are all strong risk factors in the occurrence of oral cancer, are strong sources of the free radicals. Therefore, oxidative stress is not merely a product, but a cause of oral carcinogenesis.

Other Oral Conditions

There are also a number of other oral pathologies that have been attributed to oxidative stress, including:

• Oral lichen planus (OLP): It is a chronic mucocutaneous condition of which elevated ROS levels play a role in the occurrence of epithelial apoptosis.
• Dental caries: Bacterial metabolism enhances the oxidative by-products, which result in demineralization.
• Oral mucositis: This disease is typical of patients receiving chemotherapy or radiotherapy in which the oxidative injury causes painful ulcerations.

Oral Health Chemical Processes of Antioxidants

Antioxidants are substances that neutralize the effect of oxidative damage, by donating electrons to the free radical, and thus prevent oxidative damage. The compounds act in multiple molecular pathways which keep the oral tissues in redox balance.

Enzymatic Antioxidants

Enzymatic systems are used in the human body to fight ROS. Key enzymes include:

• Superoxide Dismutase (SOD): Transforms superoxide radicals into hydrogen peroxide that is not an injurious molecule.
• Catalase (CAT): disintegrates hydrogen peroxide to water and oxygen.
• Glutathione Peroxidase (GPx): It is a lipid hydroperoxide and hydrogen peroxide reducing enzyme utilizing glutathione (GSH) as the substrate.

The enzymes are synergistic in that they help to regulate redox homeostasis in the gingival tissues and saliva.

Non-Enzymatic Antioxidants

They are minute molecules acquired either by means of diet or supplements, such as:

• Vitamin C (Ascorbic acid): It is a strong water soluble antioxidant which traps the free radicals in the saliva and the gastric fluid.
• Vitamin E (a-tocopherol): This is a lipid-soluble antioxidant that prevents lipid peroxidation of cell membranes.
• Polyphenols: The polyphenols are present in green tea, grapes, and berries and prevent the activity of inflammatory signaling (e.g. NF-kB) and decrease oxidative damage to DNA.
• Coenzyme Q10: It is part of the mitochondrial respiration and has been found to be effective in promoting periodontal healing.
• Glutathione (GSH): The great master of antioxidants in the cell that keeps the redox balance in the cell and causes the cell to be decontaminated by the xenobiotics.

Molecular Pathways

The antioxidants also control important signaling pathways of inflammation and apoptosis, which include:

• Nrf2-Keap1 Pathway: Antioxidants stimulate Nrf2 which is a transcription factor that induces the expression of antioxidant enzymes and cytoprotective genes.
• NF-kB Pathway: NF-kB activation is blocked by antioxidants and this decreases the release of the inflammatory cytokines such as IL 1b and TNF-a.
• MAPK Pathway: MAPK Signaling is a process that is used to regulate tissue repair and cellular responses to stress.

Antioxidants can destroy the tissue and promote the regeneration of the oral structures by blocking these pathways.

Foods that contain antioxidants that are good in oral health

One of the most effective natural defenses against oxidative stress is a nutrient-rich diet. There are some important antioxidant sources of oral health

Proper intake of antioxidants helps not only to strengthen gum tissues but improves the immune system in the body against pathogens in the mouth.

Dental Care Products: Antioxidants.

In addition to diet, antioxidants are also being used in increasing amounts in toothpastes, mouthwashes and periodontal gel solutions that are meant to improve oral health.

Green Tea Polyphenols and Green Tea Extracts

Green tea polyphenols are potent antioxidants and antimicrobials with epigallocatechin gallate (EGCG) being the most effective. They decrease plaque, prevent adhesion of bacteria and suppress cytokines in the tissues in the gums.

Vitamin-Enriched Toothpastes

Vitamin C and CoQ10 toothpastes are useful in the repair of the collagen and the increase of blood flow to the gums that reduces bleeding and inflammation.

Herbal Formulations

Such natural extracts as aloe vera, turmeric, and clove oil contain high amounts of antioxidants and flavonoids. These substances prevent mucosa of the mouth against oxidative damage and colonization by microbes.

Enzyme-Enhanced Products and Probiotics

The new generation oral care compounds are a combination of antioxidants, enzymes and probiotics that restore microbial balance as well as mitigate oxidative load – providing a holistic solution to oral health management.

Execution of Clinical Implications and Future Perspectives

Antioxidants are becoming an ever more popular subject of scientific interest in terms of their potential to treat oral diseases. It has been proven in clinical studies:

• Less periodontal pocket depth and higher level of attachment after antioxidant supplementation.
• Reduced saliva oxidative biomarkers following the use of dental products enriched with antioxidants.
• Improved tissue healing and decreased inflammation in patients receiving antioxidants treatment.

New studies are centered on nanotechnology-based systems of delivery where antioxidants can be incorporated into nanoparticles that can be delivered to periodontal pockets or oral lesions. This guarantees long acting and increased bioavailability.

Moreover, the use of antioxidants to supplement standard therapeutic practices such as scaling, root planing, or chemotherapy has been shown to have synergistic effects with regard to reducing oxidative side effects and hastening tissue healing.

Conclusion

Oral health depends on the balance of the oxidative stress and the antioxidant defense. Oral pathology Excessive free radicals play a role in the pathogenesis of the most significant oral diseases – periodontitis to oral cancer – due to its damage to DNA, inflammation, and tissue destruction.

Antioxidants, by diet or incorporated into products of oral care, neutralize such effects at the molecular level. They can be used as preventive and therapeutic agents in the maintenance of oral health by regulating redox pathways, inflammatory responses and facilitating tissue regeneration.

The advocacy of antioxidant-based nutrition and the use of antioxidant-based dentistry products is an evidence-based strategy toward long-term oral health. Antioxidants are potentially crucial in the future of personalized dental care as more studies are being conducted to reveal their molecular mechanisms.