Melatonin as a Candidate Therapeutic Drug for Protecting Bone Cells From Chlorhexidine-Induced Damage

Background: Melatonin was proposed for use in periodontitis and peri-implantitis therapy due to its bonesupportive effects. This issue is of interest because standard adjuvant antiseptics, namely chlorhexidine (CHX), prove damaging for osteoblasts. Thus, the aim of this study is to investigate if melatonin is suitable as an auxiliary agent for protecting osteoblasts from CHX damage. Methods: MC3T3 osteoblast response was determined following administration of various CHX concentrations in the absence or presence of melatonin. Osteoblast morphology was evaluated, total reactive oxygen species (ROS) and superoxide levels were quantified, ratios of apoptotic and necrotic cells were identified by flow cytometry, metabolic activity of remaining cells was assessed, and effects were calculated with repeated measures analysis and post hoc P value adjustment. Results: CHX led to poor morphology, increased total ROS and superoxide levels, and rigorously diminished the number of vital and metabolic active osteoblasts in a concentration-dependent manner. However, simultaneous melatonin supply supported cell morphogenesis and growth, reduced ROS and superoxide generation, shifted the percentage of CHX-damaged cells from necrotic/late to early apoptotic events, and modulated metabolic activity in osteoblasts. Conclusion: These data reveal that melatonin protects osteoblasts in the CHX context, thereby implicating melatonin as a promising drug in periodontitis and peri-implantitis treatment.