title: Melatonin as a candidate therapeutic drug for protecting bone cells from chlorhexidine-induced damage.
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.
  
  
  CONCLUSIONS
  These data reveal that melatonin protects osteoblasts in the CHX context, thereby implicating melatonin as a promising drug in periodontitis and peri-implantitis treatment.
authors.affiliation: Department of Operative Dentistry and Periodontology, Center for Dental Medicine, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Proksch
authors.forename: Sabrina Lydia
authors.initials: SL
authors.lastname: Strobel
authors.forename: Kirstin
authors.initials: K
authors.lastname: Vach
authors.forename: Thaer
authors.initials: T
authors.lastname: Abouassi
authors.forename: Pascal
authors.initials: P
authors.lastname: Tomakidi
authors.forename: Petra
authors.initials: P
authors.lastname: Ratka-Krüger
authors.forename: Elmar
authors.initials: E
authors.lastname: Hellwig
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000891:Anti-Infective Agents, Local / Q000008:administration & dosage / Q000009:adverse effects*; D000975:Antioxidants / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002710:Chlorhexidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D008550:Melatonin / Q000627:therapeutic use*; D051379:Mice; D009336:Necrosis; D010006:Osteoblasts / Q000187:drug effects*; D020011:Protective Agents / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000032:analysis; D013481:Superoxides / Q000032:analysis
chemical_list: D000891:Anti-Infective Agents, Local; D000975:Antioxidants; D020011:Protective Agents; D017382:Reactive Oxygen Species; D013481:Superoxides; D008550:Melatonin; C010882:chlorhexidine gluconate; D002710:Chlorhexidine
keywords: Cell death; cell respiration; chlorhexidine; melatonin; osteoblasts; reactive oxygen species