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 Table of Contents  
ORIGINAL HYPOTHESIS
Year : 2021  |  Volume : 12  |  Issue : 2  |  Page : 96-98

Topical Oral Melatonin Application Could Potentially Reduce the Risk of Orthodontic Appliance-Induced Periodontal Deterioration


1 Department of Dentistry, Bharathirajaa Hospital and Research Institute, T Nagar, Chennai, India
2 Department of Periodontics, Tagore Dental College and Hospital, Chennai, India
3 Cranio Facial Clinic (P) Ltd., Chennai, India
4 Department of Pedodontics and Preventive Dentistry, Tagore Dental College and Hospital, Chennai, India
5 Department of Oral Pathology and Microbiology, Sri Venkateswara Dental College and Hospital, Chennai, India
6 Department of Conservative Dentistry, Sathyabama Dental College and Hospital, Chennai, India

Date of Submission19-Aug-2020
Date of Decision20-Aug-2020
Date of Acceptance08-Sep-2020
Date of Web Publication26-Jul-2021

Correspondence Address:
Thodur Madapusi Balaji
Department of Dentistry, Bharathirajaa Hospital and Research Institute, T Nagar, Chennai
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/denthyp.denthyp_125_20

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  Abstract 


Introduction: Although patients derive numerous aesthetic and functional benefits by wearing orthodontic appliances, they also undergo some adverse changes in the oral cavity such as chronic generalized marginal gingivitis and localized gingival enlargements that can be concerning. Salivary changes following placement of fixed orthodontic appliances have been documented by numerous research papers. The Hypothesis: Melatonin in the form of an orabase gel with 1% to 2% concentration applied daily topically on the gingival tissues throughout the orthodontic treatment phase could boost the salivary antioxidant levels, neutralize the nickel and chromium toxicity, potentially attenuating inflammation, and fibrotic enlargements of the periodontal tissue. Evaluation of the Hypothesis: Testing the abovementioned hypothesis will involve a randomized double-blinded clinical trial with a placebo and test orabase gel with 1% to 2% melatonin as an active drug agent. Testing and validating the proposed hypothesis will throw open a new vista in using melatonin as a topical adjuvant in orthodontic appliance wearers.

Keywords: Melatonin, fixed orthodontic therapy, periodontal disease


How to cite this article:
Balaji TM, Jagannathan R, Murukesan S, Rajendran S, Sridhar LP, Varadarajan S, Rajendiran D. Topical Oral Melatonin Application Could Potentially Reduce the Risk of Orthodontic Appliance-Induced Periodontal Deterioration. Dent Hypotheses 2021;12:96-8

How to cite this URL:
Balaji TM, Jagannathan R, Murukesan S, Rajendran S, Sridhar LP, Varadarajan S, Rajendiran D. Topical Oral Melatonin Application Could Potentially Reduce the Risk of Orthodontic Appliance-Induced Periodontal Deterioration. Dent Hypotheses [serial online] 2021 [cited 2021 Oct 17];12:96-8. Available from: http://www.dentalhypotheses.com/text.asp?2021/12/2/96/322517




  Introduction Top


With a global increase in the prevalence of malocclusion, the number of patients needing fixed appliance therapy is also on a steady rise.[1] Although patients derive numerous aesthetic and functional benefits by wearing orthodontic appliances, they also undergo some adverse changes in the oral cavity that can be concerning. Salivary changes following placement of fixed orthodontic appliances have been documented by numerous research papers.[2],[3] It is noteworthy that nickel and chromium ions leach out into the saliva from the components of the orthodontic appliance. Clinical studies have demonstrated a significant elevation in nickel and chromium concentrations in saliva following fixed appliance therapy.[4] The increasing levels of metals do eventually subside, although their presence even temporarily has the potential to increase oxidative stress in the saliva. Several studies have demonstrated an elevation of free radicals and reactive oxygen species such as thiobarbituric acid reactive substances (TBARS) in the saliva of orthodontic appliance wearers.[5] Another significant change in saliva brought about by orthodontic therapy is the elevation of Bisphenol A from the adhesives used to fix the orthodontic brackets.[6] All the abovementioned salivary changes along with high plaque scores[7] and the presence of some putative periodontal pathogens[8] could potentially induce periodontal diseases in patients undergoing orthodontic treatment.

Orthodontic therapy has found to increase the prevalence of chronic generalized marginal gingivitis[9] and localized gingival enlargements[10] that have an inflammatory and fibrotic component needing surgical excision. Hence, the patients wearing fixed orthodontic appliances frequently approach periodontal specialists for professional scaling to remove plaque and calculus deposits and gingivectomy to excise the gingival enlargements that cause aesthetic and functional concern.

Melatonin a potent antioxidant, immunomodulator, and antifibrotic agent

Melatonin is an indoleamine hormone secreted predominantly by the pineal gland[11] and other somatic tissues including the salivary glands[12] and gingival tissues[13]. This molecule chemically denoted as N acetyl 5 methoxy tryptamine has a spectrum of functions in the human body such as the monitoring of circadian rhythm and the biological clock.[14] Other than its major function mentioned above, melatonin is a potent antioxidant molecule and can mitigate the deleterious effect of many lethal free radicals such as TBARS, hydroxyl radical, and superoxide anion.[15] It is an excellent immunomodulator and can control the production of proinflammatory cytokines such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor by inhibiting the transcription factor nuclear factor kappa B (NF κ B).[16] In addition to these roles, melatonin has been found to negate toxicity caused by metal ingestion in vital organs.[17] Another function of melatonin that has been proven is its antifibrotic effects.[18]


  The Hypothesis Top


Melatonin in the form of an orabase gel with 1% to 2% concentration applied daily topically on the gingival tissues throughout the orthodontic treatment could boost the salivary antioxidant levels, neutralize the nickel and chromium toxicity, potentially attenuating inflammation, and fibrotic enlargements of the periodontal tissue. Since melatonin in topical form has good penetration into tissues[19] and minimal or no toxic effects as a local drug delivery form, its benefits could be easily exploited in patients who need fixed orthodontic appliance therapy to achieve optimal periodontal health. 1% melatonin as topical application has already been tested in clinical intervention studies for management of periodontal disease in diabetic subjects.[20],[21] No toxic effects of the gel or oral adverse effects have been documented in the abovementioned studies. In fact, the formulation of 1% melatonin has found to reduce the salivary levels of bone metabolism markers such as osteocalcin, osteopontin, acid phosphatase, and alkaline phosphatase and has found to increase the levels of osteoprotegrin which contributes to positive bone turnover.[20] In another study, topical application of melatonin on the gingival tissues has been found to reduce serum levels of IL 6 and C reactive protein, which are markers of inflammation.[21] Hence, considering the positive beneficial effects of melatonin in periodontal homeostasis, it would definitely be worthwhile trying it as a topical formulation in orthodontic appliance wearers with increased risk of periodontal deterioration.


  Evaluation of the Hypothesis Top


Testing the abovementioned hypothesis will involve a randomized double-blinded clinical trial with a placebo and test orabase gel with 1% to 2% melatonin as an active drug agent. Briefly, the participants who are age and gender matched will be recruited into the study after obtaining their informed consent. The participants will be undergoing fixed appliance orthodontic therapy with a standardized orthodontic system that will be uniformly placed in all participants. After randomization, one group of participants will receive a test melatonin orabase gel to be applied topically twice a day throughout the treatment phase, while the other group will receive a placebo gel without melatonin. The parameters that will be measured at baseline immediately following placement of appliance, 15 days, 1 month, 3 months, 6 months, and 1 year would be salivary nickel, chromium, and bisphenol A levels. Salivary total antioxidant capacity will also be measured in the stipulated time intervals mentioned above. Clinical examination will be done to assess gingival inflammation and enlargement using standardized clinical indices. Statistical analysis of the results obtained in the placebo and test groups will be estimated. This study will be done by the team of researchers involved in the present publication. Collaboration could be attained with many clinics and teaching institutions. A multicentric trail with abundant sample size would definitely be needed to assess the beneficial periodontal effects of melatonin topical gel. If larger studies generate positive results, melatonin gel could be used as a topical perioceutical agent in routine periodontal management as an adjuvant to boost salivary antioxidant defense and control gingival inflammation. Testing and validating the proposed hypothesis will throw open a new vista in using melatonin as a topical adjuvant in orthodontic appliance wearers.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Alhammadi MS, Halboub E, Fayed MS, Labib A, El-Saaidi C. Global distribution of malocclusion traits: a systematic review. Dental Press J Orthod 2018;23:40.e1-e10.  Back to cited text no. 1
    
2.
Alessandri Bonetti G, Incerti Parenti S, Garulli G, Gatto MR, Checchi L. Effect of fixed orthodontic appliances on salivary properties. Prog Orthod 2013;14:13.  Back to cited text no. 2
    
3.
Arab S, Nouhzadeh Malekshah S, Abouei Mehrizi E, Ebrahimi Khanghah A, Naseh R, Imani MM. Effect of fixed orthodontic treatment on salivary flow, pH and microbial count. J Dent (Tehran) 2016;13:18–22.  Back to cited text no. 3
    
4.
Amini F, Rakhshan V,, Mesgarzadeh N. Effects of long-term fixed orthodontic treatment on salivary nickel and chromium levels: a 1-year prospective cohort study. Biol Trace Elem Res 2012;150:15–20.  Back to cited text no. 4
    
5.
Buczko P, Knaś M, Grycz M, Szarmach I, Zalewska A. Orthodontic treatment modifies the oxidant-antioxidant balance in saliva of clinically healthy subjects. Adv Med Sci 2017;62:129–35.  Back to cited text no. 5
    
6.
Moreira MR, Matos LG, de Souza ID, Brigante TA, Queiroz ME, Romano FL et al. Bisphenol A release from orthodontic adhesives measured in vitro and in vivo with gas chromatography. Am J Orthod Dentofacial Orthop 2017;151:477–83.  Back to cited text no. 6
    
7.
Klukowska M, Bader A, Erbe C, Bellamy P, White DJ, Anastasia MK et al. Plaque levels of patients with fixed orthodontic appliances measured by digital plaque image analysis. Am J Orthod Dentofacial Orthop 2011; 139:4e463–70.  Back to cited text no. 7
    
8.
Naranjo AA, Triviño ML, Jaramillo A, Betancourth M, Botero JE. Changes in the subgingival microbiota and periodontal parameters before and 3 months after bracket placement. Am J Orthod Dentofacial Orthop 2006;130:275.e17-22.  Back to cited text no. 8
    
9.
Baricevic M, Mravak-Stipetic M, Majstorovic M, Baranovic M, Baricevic D, Loncar B. Oral mucosal lesions during orthodontic treatment. Int J Paediatr Dent 2011;21:96-102.  Back to cited text no. 9
    
10.
Pinto AS, Alves LS, Zenkner JEDA, Zanatta FB, Maltz M. Gingival enlargement in orthodontic patients: effect of treatment duration. Am J Orthod Dentofacial Orthop 2017;152:477-82.  Back to cited text no. 10
    
11.
Reiter RJ. Pineal melatonin: cell biology of its synthesis and of its physiological interactions. Endocr Rev 1991;12:151-80.  Back to cited text no. 11
    
12.
Shimozuma M, Tokuyama R, Tatehara S, Umeki H, Ide S, Mishima K et al. Expression and cellular localization of melatonin synthesizing enzymes in rat and human salivary glands. Histochem Cell Biol 2011;135:389–96.  Back to cited text no. 12
    
13.
Balaji TM, Rao SR. Preliminary evaluation of human gingiva as an extrapineal site of melatonin biosynthesis in states of periodontal health and disease. J Clin Diagnos Res 2018;12:ZF01-ZF07.  Back to cited text no. 13
    
14.
Cagnacci A. Influences of melatonin on human circadian rhythms. Chronobiol Int 1997;14:205-20.  Back to cited text no. 14
    
15.
Teixeira A, Morfim MP, de Cordova CA, de Lima VR, GeczynskiPasa TB. Melatonin protects against pro oxidant enzymes and reduces lipid peroxidation in distinct membranes induced by the hydroxyl and ascorbyl radicals and by peroxynitrite. J Pineal Res 2003;35:262-68.  Back to cited text no. 15
    
16.
Choi EY, Jin JY, Lee JY, Choi JI, Choi IS, Kim SJ. Melatonin inhibits Prevotella intermedia lipopolysaccharide-induced production of nitric oxide and interleukin-6 in murine macrophages by suppressing NF-κB and STAT1 activity. J Pineal Res 2011;50:197-206.  Back to cited text no. 16
    
17.
Xu SC, He MD, Zhong M, Zhang YW, Wang Y, Yang L et al. Melatonin protects against Nickel-induced neurotoxicity in vitro by reducing oxidative stress and maintaining mitochondrial function. J Pineal Res 2010;49:86-94.  Back to cited text no. 17
    
18.
Gómez-Florit M, Ramis JM, Monjo M. Anti-fibrotic and anti-inflammatory properties of melatonin on human gingival fibroblasts in vitro. Biochem Pharmacol 2013;86:1784-90.  Back to cited text no. 18
    
19.
Masters A, Pandi-Perumal SR, Seixas A, Girardin JL, McFarlane SI. Melatonin, the hormone of darkness: from sleep promotion to ebola treatment. Brain Disord Ther 2014;4:1000151.  Back to cited text no. 19
    
20.
Cutando A, López-Valverde A, de Diego RG, de Vicente J, Reiter R, Fernández MH et al. Effect of topical application of melatonin to the gingiva on salivary osteoprotegerin, RANKL and melatonin levels in patients with diabetes and periodontal disease. Odontology. 2014;102:290-96.  Back to cited text no. 20
    
21.
Cutando A, Montero J, Gómez-de Diego R, Ferrera MJ, Lopez-Valverde A. Effect of topical application of melatonin on serum levels of C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in patients with type 1 or type 2 diabetes and periodontal disease. J Clin Exp Dent 2015;7:e628-33.  Back to cited text no. 21
    




 

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