SALIVARY ANTIOXIDANTS

The oral cavity is under constant bombardment from food and drink, as well 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 stress.

Saliva provides a natural defense against bacteria and other substances harmful to health. Research is confirming that antioxidants are among the most important elements in saliva, and that they help protect against oral diseases including cancer and are vital to tissue health and healing.

Composition of Saliva

Saliva is the clear, viscous fluid secreted by the three pairs of major salivary glands.  It is 98 percent water, and the remaining two percent includes proteins, electrolytes, enzymes, hormones, and other substances.

One of the major functions of saliva is digestion. The liquid and the enzymes soften food and begin the process of breaking it down.

Saliva is also important in maintaining oral health. It lubricates the teeth and tongue, and helps wash away particles of food. Although saliva can harbor bacteria and other microorganisms, it also has natural antibacterial compounds, including thiocyanate, hydrogen peroxide and immunoglobulin A.

Human saliva is rich in antioxidant compounds. The primary antioxidants include uric acid, albumin, ascorbic acid, glutathione and antioxidant enzymes. In addition, because saliva reflects the body’s levels of various hormonal, immunological, toxicological and infectious disease markers, it is an excellent tool for monitoring oral and systemic health. 

Antioxidants in Saliva

Antioxidants are critical to the body’s defense system. They neutralize free radicals, including reactive oxygen species (ROS) and reactive nitrogen species (RNS), that can cause oxidative stress leading to cell breakdown, tissue damage and DNA mutations. Antioxidants have also been shown to promote the wound-healing process and to limit the body’s release of certain inflammation-causing proteins.

Saliva, Pathogen Control and Host Tissue Response

Recent thinking in dental medicine has focused on two interrelated mechanisms by which saliva and its components, including antioxidants, maintain health in the oral cavity. One mechanism is pathogen control; another is host tissue response management.

Pathogen control is the reduction of bacteria and other harmful microorganisms. Saliva contains natural components that are anti-microbial, attacking some pathogens as they enter the oral cavity before they can take effect.

For other bacteria, such as porphyromonas gingivalis, a major cause of periodontal disease, the body’s defensive  response triggers the release of chemicals that bring about inflammation, including cytokines (e.g., interleukin 8), chemokines, prostaglandins, and destructive enzymes such as MMPs (matrix metalloproteinases). These pro-inflammatory mediators signal for an increase in the number and activity of polymorphonuclear neutrophils (PMNs), i.e., white blood cells. As the PMNs attack and ingest the bacteria, they release additional cytokines and in doing so create large quantities of ROS. This inflammatory process is the host’s response to  pathogens, but also to foreign or toxic substances such as alcohol, nicotine, medications, and even dental materials such as metals or bonding agents.

As this inflammatory host tissue response continues, the build-up of ROS leads to oxidative stress which is associated with cellular deterioration, tissue breakdown, and even DNA damage. Saliva is believed to be crucial to the body’s management of this aggressive defensive reaction. Specifically, antioxidants neutralize the ROS, counteracting the oxidative stress and its subsequent cascade of cellular, DNA and tissue damage. However, the body’s normal supply of antioxidants is diminished as it continues to neutralize ROS. The levels of natural antioxidants in saliva also diminish as part of the aging process. 

Total Antioxidant Capacity vs. Inflammation Markers

Saliva can be measured for its total antioxidant capacity (TAC), that is, the level of available antioxidants.  Specific studies have linked low levels of oral antioxidants, i.e. low TAC, to inflammatory oral conditions including periodontal disease, peri-implant disease, oral lichen planus and aphthous ulcers, dental caries, xerostomia, and oral cancer.

Similarly, oral inflammation can be measured by agents known as “inflammation markers,” notably, 8-hydroxy-deoxyguanosine(8-OHdG).  This marker is used routinely in peer-reviewed studies to assess oxidative stress.

8-OHdG↑ TAC↓

Study after study has compared the levels of inflammation markers and TAC in oral disease. Regardless of the source of the inflammation, research shows that high levels of inflammation markers are accompanied by low TAC levels. 

Polyphenol Antioxidants

Polyphenols, a class of antioxidants that are derived from fruits, vegetables and other plant sources, have strong support in published scientific research. A literature review concluded  that polyphenol antioxidants can inactivate periodontal pathogens and have a preventive effect against oral cancer.

Polyphenol antioxidants are believed to be involved in the host’s tissue response in three ways.

1) Antioxidants can reduce the white blood cells’ production of cytokines and chemokines, the pro-inflammatory proteins that are responsible for breaking down cells and other structures.

2) Antioxidants neutralize ROS, protecting fibroblasts from toxic substances that release ROS. and reversing oxidative stress.

3) Antioxidants have been shown to promote wound healing.

However, in the process of managing the host tissue response, antioxidants are depleted. This is demonstrated by the reduction of TAC concomitant to the increase in inflammatory markers. The preponderance of research studies points to the conclusion that in order to manage the host tissue response, “Administration of local antioxidants to the oral cavity should be considered.” (Hershkovich, Gerontology 2007).

A scientific study published in 2013 showed that polyphenols applied to the oral cavity work together with saliva, red blood cells, platelets and some microorganisms to decompose ROS. Moreover, it was shown that polyphenol antioxidants “avidly adhere to mucosal surfaces, are retained there for long periods and may function as ‘slow-release devices’ capable of affecting the redox status in the oral cavity.” In other words, not only do polyphenol antioxidants work in concert with saliva and its components, polyphenols provide a long-lasting defense against free radicals in the oral cavity. “Therefore a steady, slow release of antioxidant polyphenols retained in the oral cavity might be beneficial to cope with tissue damage.” (Ginsburg, PLoS One 2013.)

Clinical studies of daily use of topical oral antioxidants have also corroborated the understanding that amplifying the levels of antioxidants in the oral cavity can reverse damage to soft tissue caused by the host’s defensive tissue reactions.

 

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