Toxic effect of rifampicin on human osteoblast-like cells.
We examined the effects of rifampicin on osteoblast-like cells derived from adult human bone in vitro. Cancellous bone was collected from five different individuals during elective orthopaedic operations and cultured in antibiotic-free media. Total DNA, 3H-thymidine incorporation and alkaline phosphatase (ALP) activity were measured after the cells were cultured for 4 days in media containing concentrations of rifampicin ranging from 0 to 1000 microg/ml. Mean total DNA was decreased at concentrations of 10 microg/ml and above in the cultures obtained from four out of five individuals but these decreases were significant in the cultures from only two individuals. 3H-thymidine incorporation, a more sensitive indicator of change in cell proliferation, and ALP activity were significantly decreased (P < 0.05) in all of the cultures containing 3 and 7 microg/ml, respectively. In the clinical setting, serum concentrations of rifampicin often exceed 10 microg/ml after systemic administration. The present study has shown that rifampicin, at these concentrations, can inhibit the proliferation of osteoblast-like cells in vitro. Further studies should be carried out to assess whether rifampicin is detrimental to the bone repair process in vivo.
Isefuku
S
S
Nuffield Department of Orthopaedic Surgery, Nuffield Orthopaedic Centre, Headlington, Oxford, UK.
Joyner
C J
CJ
Simpson
A H
AH
D000293:Adolescent; D000368:Aged; D000904:Antibiotics, Antitubercular / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D005269:Femur / Q000166:cytology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D012293:Rifampin / Q000633:toxicity*; D013936:Thymidine / Q000493:pharmacokinetics; D014316:Tritium
D000904:Antibiotics, Antitubercular; D014316:Tritium; D013936:Thymidine; D012293:Rifampin