Chlorhexidine effects on membrane lipid domains of human buccal epithelial cells.
The effect of chlorhexidine gluconate on the adherence of Candida albicans to human buccal epithelial cells (BEC) and drug-induced alterations in BEC membrane-lipid packing order were examined. Treatment of BEC with attached yeasts with 0.1 and 0.2% chlorhexidine resulted in significant yeast detachment after 90 and 60 min, respectively. Following pre-treatment of BEC with greater than 0.1% chlorhexidine, yeast adherence was inhibited by greater than 80%. In parallel experiments, the fluorescence anisotropy of BEC labeled with fluorescent membrane probes--diphenylhexatriene (DPH) and trimethylammonium DPH--was assessed following exposure to chlorhexidine. The fluorescence anisotropy decreased with increasing concentrations of chlorhexidine, which indicated that the drug decreased epithelial-cell membrane-lipid packing order. Chlorhexidine concentrations that altered epithelial-cell membrane-lipid packing order, particularly in superficial regions, were similar to those drug concentrations required for detachment of adherent yeasts. Similar results were obtained with a second antifungal, nystatin A. While the effects of chlorhexidine on the buccal-cell membrane-lipid packing order were not reversed by multiple washings, the opposite situation occurred with nystatin A. The results suggest that chlorhexidine-induced alterations of BEC membrane-lipid order may be involved in the antifungal actions of the drug.
Audus
K L
KL
Department of Pharmaceutical Chemistry, School of Pharmacy, University of Kansas, Lawrence 66045.
Tavakoli-Saberi
M R
MR
Zheng
H
H
Boyce
E N
EN
D000935:Antifungal Agents / Q000494:pharmacology*; D001667:Binding, Competitive; D002176:Candida albicans / Q000187:drug effects*; D002448:Cell Adhesion / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects / Q000382:microbiology* / Q000648:ultrastructure; D002478:Cells, Cultured; D002710:Chlorhexidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004161:Diphenylhexatriene; D004847:Epithelial Cells; D005454:Fluorescence Polarization; D006801:Humans; D008563:Membrane Lipids / Q000502:physiology; D008855:Microscopy, Electron, Scanning; D009061:Mouth Mucosa / Q000166:cytology; D009761:Nystatin / Q000494:pharmacology; D013172:Spores, Fungal / Q000187:drug effects
D000935:Antifungal Agents; D008563:Membrane Lipids; D009761:Nystatin; D004161:Diphenylhexatriene; C010882:chlorhexidine gluconate; D002710:Chlorhexidine