Oral mucositis is a prevalent sequella of chemotherapy and radiation treatment of head and neck cancers and bone marrow transplantation, often leading to cessation of cancer treatment due to the debilitating and morbid effects this acute inflammatory response of the oral mucosa has on the cancer patient.
Approximately 40% of patients who receive chemotherapy, and virtually all patients who have head and neck cancers and are treated with radiation develop oral mucositis (REF). Oral mucositis is an inflammation of the mucosa of the mouth and throat that ranges from redness to severe ulceration. Chemotherapy and radiation treatment also suppress the patient’s immune system; therefore, when the integrity of oral mucosa and immunity is compromised there is increased risk of secondary and opportunistic infections including candidiasis in the cancer patient. The oral tissue reaction to chemical or radiation stimuli during cancer treatment provokes a complex inflammatory reaction in the vascularized connective tissue of the oral mucosa that leads to oral mucositis. More importantly, preexisting conditions, such as periodontal disease or gingivitis, may also rapidly progress to oral mucositis. The inflammatory response results in various stages of tissue sloughing, ulceration and pain for the patient. The vascular and cellular responses involved in the acute and chronic inflammatory reaction to these stimuli are mediated by chemical factors, such as cytokines/chemokines and eicosanoids, induced by the disrupted or activated oral tissue cells. These chemical mediators, either alone or in combination, may initiate and exacerbate oral mucosa inflammation resulting in cell necrosis and/or tissue damage. Combined, all of these factors may trigger a vicious cycle of inflammatory mediator release and oral mucosal tissue damage. Prevention and treatment of oral mucositis are vital in increasing the quality of life and decreasing cost of care of patients receiving chemotherapy and radiation treatment.
Prevention Oncology Mouth Rinse targets the inflammatory response in the oral tissue induced by chemotherapy and/or gamma radiation. Prevention Oncology Mouth Rinse’s glycerin-based formula allows prophylaxis and/or therapeutic treatment without causing further damage to the oral mucosa or resident microflora. Additionally, Prevention Oncology Mouth Rinse’s formula may promote the normal metabolic processes of oral mucosa tissue cells necessary for tissue healing. Briefly, the antibacterial properties of glycerin, in combination with the Oncology Mouth Rinse’s oxidant cation-anion species, react providing antifungal and antiviral properties resulting in a microenvironment free of pathogenic microbes, supporting healing of the ulcerated tissue. Drake et al., documents the antimicrobial activity of Prevention Mouth Rinse containing the same glycerin-based formula, against numerous oral microbes such as Streptococci and Candid albicans (REF). Prevention Mouth Rinse showed rapid and potent antimicrobial activity against all microorganisms tested in the study (REF). The high oxygen content of Prevention Oncology Mouth Rinse may also serve as a source of oxygen molecules that serve as electron acceptors for flavoproteins in the oral tissue cells; thereby maintaining the balance of peroxisome biogenesis needed to sustain the balance of amino acid synthesis and nitrogen levels in the tissue cells. Glycerin, by its molecular structure, may react in or support the biochemical pathways involved in the elimination of excess amino acid nitrogen levels from tissue cells. Combined, the molecular formula of Prevention Oncology Mouth Rinse may prevent or inhibit cell necrosis and mucosa disruptions.
The patented and proprietary formula of Prevention Oncology Mouth Rinse is based on glycerin, menthol, peppermint oil, salts and oxygen. When blended together in concise concentrations, Prevention Oncology Mouth Rinse may block the chemical inflammatory mediators found in oral tissue cells and the surrounding area, such as eicosanoids from arachidonic acid metabolism, histamine, bradykinin, and substance P, induced by stimuli from chemotherapy and gamma radiation treatment.
Arachidonic acid is a 20-carbon polyunsaturated fatty acid present in the phospholipids (phosphatidylcholine, phosphatidylinositol and phosphatidylethanolamine) of cellular membranes. Arachidonic acid is released from the phospholipids membrane following physical, mechanical or chemical stress to the cell such as chemotherapy or radiation. Once released from the cellular membrane, arachidonic acid serves as a precursor for eicosanoid biosynthesis leading to the production of leukotrienes (LT), prostaglandins (PG), prostacyclins, and thromboxanes (TxB). Two main classes of enzymes, cyclooxyngenases and lipooxygenases, are responsible for eicosanoid biosynthesis with lipooxygenases involved in LT production and cyclooxyngenases catalyzing PG, TxB and prostacylin synthesis. Eicosanoids are intricately involved in controlling inflammation, immunity, and pain response in the central nervous system. Briefly, in the inflammatory response, prostaglandins, thromboxanes and leukotrienes result in vasoconsriction (PGI2 and TXA2) and vasodilation (PGE2 and LTB4), LTB4 mediates swelling due to increased vascular permeability, and PGE2 results in both pain and heat at the site of trauma as well as the fever response. Cyclooxygenases (COX-1 and COX-2) are the enzymes involved in the production of PGs from arachidonic acid. Cytokines involved in inflammation increase COX-2 enzymatic activity thereby increasing PG synthesis. Common over the counter medications used to treat pain, fever, and swelling block the COX-2 pathways limiting eicosanoid production.
The Prevention Oncology Mouth Rinse formula may also support a use as a therapeutic treatment option to combat inflammation associated with oral mucositis. Chemically complexed zinc ion, when mixed with sodium and citrate ions, may permeate the cellular membrane and positively alter the metabolic function of the cell. The positive charge of the zinc ion may switch the electrical field of the cellular membrane from a neutral to a positive state, inhibiting or blocking the release of arachidonic acid from the phospholipid membrane and thus halting eicosanoid biosynthesis. In addition, the formula’s blend of salts and oxidants may affect the synthesis and activity of the cyclooxygenase and lipooxygenase enzymes thereby suppressing prostaglandin and leukotriene production and the inflammatory reaction. When zinc chloride, sodium citrate, and glycerin react with an oxidant, this oxidant compound may block the production of inflammatory mediators from cells within the oral tissue inflammatory microenvironment. When the four salts comprising the Oncology Mouth Rinse combine and incubate, the ions separate in an aqueous environment providing four free ions to react giving a chemical structure allowing bonding to oxidant species. As a result, in combination with glycerin, Prevention Oncology Mouth Rinse may also alter the enzymatic activity of elastase, another enzyme important in the control of inflammation by changing the enzymatic functional groups. The hydrolysis of an ester or an amide during enzymatic activity of elastase is to replace water by a stronger nucleophylic group that is part of the enzyme’s active site. The two-step pathway that occurs in this process requires that the intermediate be more susceptible to nucleophilic attack by water than the original ester or amide. Nucleophilic groups on enzymes participate in a variety of other types of reactions in addition to hydrolytic reactions. Changing the nucleophylic group to an electrophylic group may impede the production of the inflammatory mediators produced by elastase. Additionally, we hypothesize that the positive-charged zinc ions, when mixed with the salts and oxidant in Oncology Mouth Rinse, react with carbonyl oxygen atoms of the aldehyde or peptide substrates in the active inflammatory site within the oral cavity, also disrupting production of the inflammatory mediators that are responsible.
Furthermore, we postulate that Prevention Oncology Mouth Rinse accelerates the natural repair process of the tissue cell thru balancing of cellular metabolic processes due to the biochemical nature of the Oncology Rinse formula. The main chemical component of glycerin, glycerol, C3H5 (OH) 3, a trihydric alcohol, provides two primary and one secondary hydroxyl group as potential reaction sites for the cations and anions in Prevention Oncology Mouth Rinse. Glycerin’s molecular structure may also react with the menthol molecular structure, C10H19OH. The chemical structures hypothesized above may provide a rich source of oxygen molecules, thus raising the transcutaneous oxygen tension in the tissue cells and promoting tissue healing.
Menthol, a cyclic monoterpene, is the primary chemical component of peppermint oil, and when mixed with glycerin in precise concentrations, has significant clinical applications (REF). Menthol’s three asymmetric carbon atoms, structured in a cyclohexane ring, yield four pairs of optical isomers. One of these optical isomers, 1-menthol, may exhibit a cooling sensation when applied to skin or the oral mucosa. The glycerin-menthol blend comprising Prevention Oncology Mouth Rinse, reacting with the cations and anions (zinc, sodium, citrate, chloride) also present in the formula in proper chemical ratios, may alleviate or relieve the pain caused by tissue ulcerations and severe inflammation associated with oral mucositis.
Prevention Oncology Mouth Rinse has completed all FDA safety studies and is currently is being utilized by more than 30 Oncology Centers nationwide as both prophylactic and therapeutic treatment of oral mucositis following chemotherapy or radiation therapy. Although future research efforts are needed to define and characterize the mechanisms by which Prevention Oncology Mouth Rinse mediates its profound effects on the treatment of oral mucosal inflammation and ulceration, we believe this product is a necessity in the prevention and treatment of oral mucositis during chemotherapy and radiation treatment of head and neck cancers.