title: Effect of chlorhexidine digluconate on different cell types: a molecular and ultrastructural investigation.
abstract: Although several studies have shown that chlorhexidine digluconate (CHX) has bactericidal activity against periodontal pathogens and exerts toxic effects on periodontal tissues, few have been directed to evaluate the mechanisms underlying its adverse effects on these tissues. Therefore, the aim of the present study was to investigate the in vitro cytotoxicity of CHX on cells that could represent common targets for its action in the surgical procedures for the treatment of periodontitis and peri-implantitis and to elucidate its mechanisms of action. Osteoblastic, endothelial and fibroblastic cell lines were exposed to various concentrations of CHX for different times and assayed for cell viability and cell death. Also analysis of mitochondrial membrane potential, intracellular Ca2+ mobilization and reactive oxygen species (ROS) generation were done in parallel, to correlate CHX-induced cell damage with alterations in key parameters of cell homeostasis. CHX affected cell viability in a dose and time-dependent manners, particularly in osteoblasts. Its toxic effect consisted in the induction of apoptotic and autophagic/necrotic cell deaths and involved disturbance of mitochondrial function, intracellular Ca2+ increase and oxidative stress. These data suggest that CHX is highly cytotoxic in vitro and invite to a more cautioned use of the antiseptic in the oral surgical procedures.
authors.affiliation: Department of Oral Surgery, University of Florence, Viale Morgagni 85, 50134 Florence, Italy. dott.giannellimarco@dada.it
authors.forename: M
authors.initials: M
authors.lastname: Giannelli
authors.forename: F
authors.initials: F
authors.lastname: Chellini
authors.forename: M
authors.initials: M
authors.lastname: Margheri
authors.forename: P
authors.initials: P
authors.lastname: Tonelli
authors.forename: A
authors.initials: A
authors.lastname: Tani
mesh_terms: D000891:Anti-Infective Agents, Local / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D020013:Calcium Signaling / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002710:Chlorhexidine / Q000031:analogs & derivatives* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000648:ultrastructure; D005347:Fibroblasts / Q000187:drug effects* / Q000648:ultrastructure; D006801:Humans; D020287:In Situ Nick-End Labeling; D008564:Membrane Potentials / Q000187:drug effects; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D051336:Mitochondrial Membranes / Q000187:drug effects; D010006:Osteoblasts / Q000187:drug effects* / Q000648:ultrastructure; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000891:Anti-Infective Agents, Local; D017382:Reactive Oxygen Species; C010882:chlorhexidine gluconate; D002710:Chlorhexidine