Melatonin (N-acetyl-5-methoxytryptamine) is a hormone that is synthesized by the pineal gland. The mechanism of melatonin synthesis is initiated from pinealocytes, melatonin will be synthesized by pinealocytes then will carry free tryptophan from the blood and convert it into serotonin, which involves the enzymes tryptophan-5-hydroxylase and 5-hydroxytryptophan decarboxylase, respectively, hydroxylate and decarboxylation of tryptophan respectively. At night, serotonin is converted to N-acetylserotonin by the action of N-acetyltransferase. After that the hydroxyindole-O-methyl transferase enzyme acts on N-acetylserotonin causing methylation and then forming melatonin.2
Melatonin which is also called the "hormone of darkness" has several physiological functions in the body, including controlling circadian rhythm, regulating body temperature, activating the immune system, controlling the secretion of growth hormone and Adrenocortico Hormone, increasing osteoblast differentiation in vitro and increasing in vivo formation. and has a hypnotic action for sleep initiation as an activator to open the "sleep gate".
Melatonin levels in the body increase when a person sleeps at night. In dark light conditions, the neural electrical signals that have been received by the central nervous system will be transmitted to the pineal gland and will release norepinephrine which will initiate melatonin synthesis. The pineal gland which produces the hormone melatonin is a gland that is very sensitive to light, so this gland is active at night. Based on research, it turns out that in normal people, this metallonin hormone has increased production around 02.00-04.00 at night so that at that time the body's melatonin levels reach a maximum.
Based on the function of melatonin, melatonin levels in the body can decrease if there is inflammation in the body, increased free radicals, bone damage, immune system disorders, oxidative stress and circadian rhythm disorders.
Periodontal disease is a disease that occurs in the mouth. This disease is characterized by inflammation of the periodontium tissue which can then affect the periodontal ligament and alveolar bone. The periodontium tissue is the tissue found in the mouth consisting of gingiva, cementum, alveolar bone, and periodontal ligament. Periodontal disease is caused by the accumulation of bacteria that adhere to the surface of the teeth, especially in the area under the gingiva. Subgingival bacteria colonize to form periodontal pockets and cause further inflammation of the gingival tissue, and in advanced periodontal disease progressive alveolar bone loss occurs and if treatment is not performed it will result in tooth loss. Gingival inflammation, bacterial infection, alveolar bone damage, and subsequent tooth loss are processes of periodontal disease.
The pathogenesis of periodontal disease begins with early gingivitis, advanced gingivitis and if there is continuous inflammation it can cause periodontitis. The periodontal tissue structure when inflamed is first seen around the small gingival vessels, apical to the epithelium jungtion. The early signs of early gingivitis are plaque deposits, the initial inflammatory changes will continue with increased gingival fluid flow and PMN migration. Changes that occur in both the junction epithelium and the cravicular epithelium are a sign of cell separation and some of the proliferation of basal cells. The interdental papillae become redder and swollen and bleed easily.
Furthermore, advanced gingivitis occurs within 2-3 weeks, will form gingivitis that is even more severe. At this stage mast cells are also found. Immunoglobulins, especially IgG are found in the epithelium and connective tissue. The gingiva is red, swollen and bleeds easily. With worsening collagen breakdown and inflammatory swelling, the gingival margins can easily be removed from the tooth surface, increasing the likelihood of a gingival pocket or false pocket being identified. At this stage there has been degeneration of the epithelial cells of the junction and some have proliferated from the basal layer to the connective tissue below, but at this stage there has not been any migration of epithelial cells in large numbers to the root surface. If the inflammation has spread along the transeptal fibers, it will be seen that there is resorption of the alveolar bone crest. This absorption is reversible, especially in the recovery of inflammation.
One important sign of this disease is the absence of bacteria in the epithelium or connective tissue because the fibrous tissue is damaged in the area around the inflammation, in some areas some distance from the area of inflammation, it is seen that there is proliferation of fibrous tissue and the formation of new blood vessels. This productive restorative activity is a very important characteristic of chronic lesions and, in conditions of long-term irritation and inflammation, fibrous tissue elements will be a major component of tissue transformation. So, damage and repair could take place alternately. If the inflammation is dominant, the tissue will be red, soft and bleed easily, but if the production of fibrous tissue is dominant, the gingival will become hard and pink even though the swelling is less bleeding, or even absent.
Furthermore, periodontitis occurs and is characterized by plaque irritation and continuous inflammation, the integrity of the epithelium jungtion will be further damaged. Epithelial cells will degenarate and separate, the attachment to the tooth surface will be released. At the same time, epithelium junction will proliferate into the connective tissue and downward on the root surface if the dentogingival and apex fibers of the alveolar bone are damaged. The apical migration of epithelium junction will continue and this epithelium will detach from the tooth surface, forming a periodontal pocket or original pocket. This state is an irreversible change. If a periodontal pocket has formed, the plaque is in contact with cementum.
The epithelium of the pocket wall may remain intact or ulcerated. Tissue fluid flow and immigration from PMN will continue and presumably this tissue fluid flow helps to increase subgingival calculus deposition. Spread of inflammation to the crest of the alveolar bone. Characterized by the infiltration of cells into the trabecular spaces, areas of bone resorption and an increase in the size of the trabecular space. There is a tendency for bone resorption to be offset by deposition further away from the inflammatory site. So that the bones will experience remodeling, but still experience damage. Bone resorption starts from the interproximal area to become wide, for example between molar teeth and then if the resorption process continues, the resorption will extend laterally, so that all areas of the alveolar bone crest will be resorbed.
This disease begins with a bacterial attack, then inflammatory cells will be stimulated to release free radicals to destroy these bacteria. Excessive free radicals can damage cells in the body. With antioxidants as one of the body's defense systems, free radicals will be neutralized. The condition of the periodontium tissue is influenced by the internal antioxidants produced by the body to avoid oxidative stress, namely an imbalance of oxygen radicals and non-radicals that can damage cells by various mechanisms.
One of the etiologies of periodontal disease is the presence of reactive oxygen species stimulated by bacterial antigens.
Leukocytes are the first cells that will fight pathogenic bacteria that attack the periodontium tissue. In the early stages of periodontitis, there is an increase in PMN which at the same time will increase the release of free radicals in the phagocytosis process against infection. Patients with periodontal disease have high levels of PMN and excessive ROS (reactive oxygen species) which will cause destruction of the gingival tissue, periodontal ligaments and alveolar bone in various ways including damaging DNA and stimulating the formation of proinflammatory cytokines. This also explains that the excessive involvement of ROS is related to tissue damage to the periodontium.
The inflammatory process can cause tissue destruction of the periodontium. Initially, the PMN produced had a protective role against the periodontium tissue. However, the functionally activated PMN will show an increase in free radical production. Prostaglandin production also increases due to stimulation of gram-negative pathogenic bacteria. Enzymes such as collagenase, hyaluronidase and elastase also play a role in cell and periodontium tissue damage as a result of the working mechanism of these enzymes so that in this case it can be concluded that the immune system, phagocytosis and enzymes are factors that cause inflammation causing destruction of the periodontium tissu and cause tooth loss.