Melatonin as a candidate therapeutic drug for protecting bone cells from chlorhexidine-induced damage

J Periodontol. 2014 Dec;85(12):e379-89. doi: 10.1902/jop.2014.140279.

Abstract

Background: Melatonin was proposed for use in periodontitis and peri-implantitis therapy due to its bone-supportive 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.

Keywords: Cell death; cell respiration; chlorhexidine; melatonin; osteoblasts; reactive oxygen species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Anti-Infective Agents, Local / administration & dosage
  • Anti-Infective Agents, Local / adverse effects*
  • Antioxidants / therapeutic use*
  • Apoptosis / drug effects
  • Cell Count
  • Cell Death / drug effects
  • Cell Shape / drug effects
  • Cell Survival / drug effects
  • Chlorhexidine / administration & dosage
  • Chlorhexidine / adverse effects
  • Chlorhexidine / analogs & derivatives*
  • Dose-Response Relationship, Drug
  • Melatonin / therapeutic use*
  • Mice
  • Necrosis
  • Osteoblasts / drug effects*
  • Protective Agents / therapeutic use*
  • Reactive Oxygen Species / analysis
  • Superoxides / analysis

Substances

  • Anti-Infective Agents, Local
  • Antioxidants
  • Protective Agents
  • Reactive Oxygen Species
  • Superoxides
  • Melatonin
  • chlorhexidine gluconate
  • Chlorhexidine