Effect of Locally Delivered Melatonin as an Adjunct to Nonsurgical Therapy on GCF Antioxidant Capacity and MMP-9 in Stage II Periodontitis Patients: A Randomized Controlled Clinical Trial

Abstract

Objectives. Periodontitis is characterized by inflammatory destruction of periodontal tissue, loss of attachment, and bone resorption. The increase in reactive oxygen species (ROS) is responsible for the oxidative damage occurring in periodontal tissues. Melatonin has important immunomodulatory, anti-inflammatory, and powerful antioxidant functions. The current study was carried out to evaluate the effect of topical melatonin gel as an adjunct to nonsurgical periodontal therapy. Methods. This split-mouth randomized controlled clinical trial was performed on 24 patients with grade II periodontitis. Two sites in each patient were randomly assigned; test sites were treated by nonsurgical therapy followed by intrapocket application of 5% melatonin gel. Control sites were treated by nonsurgical therapy followed by intrapocket application of placebo gel. Both the melatonin and placebo gel were applied weekly once for four weeks. Assessment of clinical parameters (PD and CAL) was done at baseline and 3 months after therapy. Total antioxidative capacity (TAC) and matrix metalloproteinase-9 (MMP-9) levels in GCF were also evaluated utilizing commercially available enzyme-linked immunosorbent assay kits (ELISA) at baseline and 3 months after therapy. Results. Treatment with topical melatonin was associated with a reduction in periodontal inflammation reflected as an improvement in the clinical periodontal parameters. Melatonin-treated sites showed a more statistically significant percent reduction in PD and more statistically significant percent gain in CAL than the control site. Additionally, a significant increase in TAC and a significant decrease in MMP-9 levels in GCF were found in melatonin-treated sites in comparison to control sites. Conclusions. The adjunctive use of topical melatonin gel with nonsurgical periodontal therapy has potent anti-inflammatory and antioxidant activity in the treatment of grade II periodontitis patients.

Melatonin as an adjunctive treatment on dental procedures: A systematic review

“…There were different kinds of studies included in this review, and twelve of them showed that when the melatonin is administered, the periodontal disease has an improvement (Cutando et al, 2013,2014,2015; Cobo‐Vázquez et al, 2014; Marawar et al, 2014; Chitsazi et al, 2017; Montero et al, 2017; El‐Sharkawy et al, 2019; Tinto et al, 2020; Bazyar et al, 2019; Zare Javid et al, 2020; Anton et al, 2021; Ahmed et al, 2021). These studies analyzed the periodontal and gingival indexes and also the pocket depth and showed positive effects in patients that received the substance, proving that melatonin is able to interfere in the inflammatory, in anti‐oxidative process and in the repair mechanism, such as in the proliferation of the fibroblasts (Gómez‐Florit et al, 2013).…”

“…There were different kinds of studies included in this review, and twelve of them showed that when the melatonin is administered, the periodontal disease has an improvement (Cutando et al, 2013(Cutando et al, ,2014(Cutando et al, ,2015Cobo-Vázquez et al, 2014;Marawar et al, 2014;Chitsazi et al, 2017;Montero et al, 2017;El-Sharkawy et al, 2019;Tinto et al, 2020;Bazyar et al, 2019;Zare Javid et al, 2020;Anton et al, 2021;Ahmed et al, 2021).…”

“…The studies used topical melatonin in an 1% of concentration for 20 days (Cutando et al, 2013(Cutando et al, ,2014(Cutando et al, ,2015Montero et al, 2017) or 5% for 30 days (Ahmed et al, 2021). The ones that applied the melatonin systemic used it in a concentration between 1 to 6 mg daily between 30-60 days.…”

“…Twelve studies reported the effect of melatonin in periodontal disease. The periodontal patients that were treated by the conventional treatment associated with melatonin showed a decrease of the periodontal disease levels as gingival index, pocket depth, periodontal index, and bleeding on probing (Cutando et al, 2013(Cutando et al, ,2014(Cutando et al, ,2015Marawar et al, 2014, Chitsazi et al, 2017Montero et al, 2017;El-Sharkawy et al, 2019;Tinto et al, 2020;Bazyar et al, 2019;Zare Javid et al, 2020;Anton et al, 2021;Ahmed et al, 2021); Among these, some indicated the reduction of inflammatory mediators, such as alkaline phosphatase, osteocalcin (OCN), osteopontin (OPN), RANK, RANKL, TNF-a, IL-6, and prostaglandin 2 (Bazyar et al, 2019;Cutando et al, 2013Cutando et al, ,2014Cutando et al, ,2015El-Sharkawy et al, 2019;Montero et al, 2017).…”

Beneficial Effects of Melatonin on Periodontitis Management: Far More Than Oral Cavity

“…Increasing evidence from clinical trials has proved that melatonin exhibits beneficial effects for the treatment of periodontitis. For instance, local delivery of melatonin gel as an adjunct to nonsurgical periodontal therapy (NSPT) helps to provide better clinical and radiographic outcomes [ 97 , 98 ]. Systemic administration of melatonin after one-stage full mouth NSPT results in a greater clinical attachment level (CAL) gain and probing depth (PD) reduction, with reference to NSPT with placebo treatment [ 99 , 100 ].…”