Cytotoxicity of chlorhexidine on human osteoblastic cells is related to intracellular glutathione levels.
OBJECTIVE
To evaluate the mechanisms of cytotoxicity of chlorhexidine (CHX) in human osteoblastic cells in vitro.


METHODS
Cytotoxicity, cell proliferation and collagen synthesis assays were performed to elucidate the toxic effects of CHX on the human osteoblastic cell line U2OS. To determine whether glutathione (GSH) levels were important in the cytotoxicity of CHX, cells were pre-treated with 2-oxothiazolidine-4-carboxylic acid (OTZ) to boost GSH levels or buthionine sulfoximine (BSO) to deplete GSH.


RESULTS
CHX demonstrated a cytotoxic effect to U2OS cells in a dose-dependent manner (P < 0.05). The 50% inhibition concentration of CHX was approximately 0.005%. CHX also inhibited cell proliferation and collagen synthesis (P < 0.05). The addition of OTZ acted as a protective effect on the CHX-induced cytotoxicity (P < 0.05). In contrast, the addition of BSO enhanced the CHX-induced cytotoxicity (P < 0.05).


CONCLUSIONS
The levels of CHX tested inhibited cell growth, proliferation and collagen synthesis on U2OS cells. CHX has significant potential for periapical toxicity. GSH depletion might be one of the mechanisms underlying CHX cytotoxicity.
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
T-H
TH
Lee
C-C
CC
Hu
S-S
SS
Lee
M-Y
MY
Chou
Y-C
YC
Chang
D000891:Anti-Infective Agents, Local / Q000008:administration & dosage / Q000633:toxicity*; D000963:Antimetabolites / Q000494:pharmacology; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002710:Chlorhexidine / Q000008:administration & dosage / Q000633:toxicity*; D003094:Collagen / Q000096:biosynthesis / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes; D005978:Glutathione / Q000037:antagonists & inhibitors / Q000187:drug effects*; D006801:Humans; D010006:Osteoblasts / Q000187:drug effects*; D011355:Prodrugs / Q000494:pharmacology; D011761:Pyrrolidonecarboxylic Acid / Q000494:pharmacology; D053778:Thiazolidines / Q000494:pharmacology
D000891:Anti-Infective Agents, Local; D000963:Antimetabolites; D005456:Fluorescent Dyes; D011355:Prodrugs; D053778:Thiazolidines; D019328:Buthionine Sulfoximine; D003094:Collagen; D004247:DNA; D005978:Glutathione; D002710:Chlorhexidine; D011761:Pyrrolidonecarboxylic Acid; C029536:2-oxothiazolidine-4-carboxylic acid