Mechanisms underlying chlorhexidine-induced cytotoxicity.
Chlorhexidine (CLX) is the most widely used antiseptic for wound and skin disinfection. Despite its potent bactericidal action, skin irritation is observed when it is used topically. This study aimed to evaluate the mechanisms underlying CLX-induced toxicity on human dermal fibroblasts with special emphasis on factors that may mediate or counteract its undesirable effects. Cells were exposed to CLX concentrations of 0.00005-0.025% for 3, 6, 8 or 24 h in the absence or presence of different concentrations of foetal calf serum (FCS) (2, 5 and 10%). Depletion of cell ATP occurred, in a time- and concentration-dependent manner, in all experimental conditions at [CLX] >0.001%. At 24 h of CLX exposure time, the decrease in intracellular ATP was produced from a 10-times lower CLX concentration (0.0001%). Concentrations > or =0.02% produced total loss of ATP. However, cell survival was maintained after CLX treatment for 3 and 8 h and CLX concentrations > or =0.005% were required to produce total cell death. CLX exerted an inhibitory concentration-dependent effect on DNA synthesis from concentrations as low as 0.0001%. Only FCS at 10% appeared to have a cytoprotective action against CLX-induced cytotoxicity.
Hidalgo
E
E
Biochemistry & Molecular Biology Centre, Pharmacy Service, Vall d'Hebron Hospitals, Barcelona, Spain. ehidalgo@cs.vhebron.es
Dominguez
C
C
D000255:Adenosine Triphosphate / Q000378:metabolism; D000891:Anti-Infective Agents, Local / Q000633:toxicity*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002710:Chlorhexidine / Q000633:toxicity*; D004247:DNA / Q000096:biosynthesis; D020405:Dermis / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D019384:Nucleic Acid Synthesis Inhibitors / Q000633:toxicity; D013778:Tetrazolium Salts / Q000378:metabolism
D000891:Anti-Infective Agents, Local; D019384:Nucleic Acid Synthesis Inhibitors; D013778:Tetrazolium Salts; C059087:2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-((phenylamino)carbonyl)-2H-tetrazolium hydroxide; D000255:Adenosine Triphosphate; D004247:DNA; D001973:Bromodeoxyuridine; D002710:Chlorhexidine