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Gentamicin may have an adverse effect on osteogenesis
Shuji Isefuku1, Clive J Joyner, A Hamish R W Simpson
1Nuffield Department of Orthopaedic Surgery, University of Oxford, Headington, England, United Kingdom.
Objective:
To investigate the toxic effect of gentamicin at the high concentrations that can be achieved by local administration in the management of bone infection.
Design:
Randomized, prospective study in cultured cells, with drug exposure duration of 4 days.
Setting:
Cell culture in Dulbecco's modification of Eagle's minimal essential medium with supplements at 37 degrees C in air:CO2 (v:v, 95:5).
Materials:
Human osteoblastlike cells derived from cancellous bone collected from four adult patients without systemic disease during total hip replacement were cultured in antibiotic-free medium for 4 weeks.
Intervention:
The cultured cells were exposed to media containing various concentrations of gentamicin (0-1000 microg/mL) for 4 days.
Main Outcome Measurements:
Alkaline phosphatase activity, total DNA, and 3H-thymidine incorporation.
Result:
Alkaline phosphatase activity was significantly decreased (p < 0.05) in all of the cultures at gentamicin concentrations of 100 microg/mL and above. 3H-thymidine incorporation was also decreased (p < 0.05) in three out of four cultures at 100 microg/mL and above. Total DNA was significantly decreased (p < 0.05) at 700 microg/mL and above.
Conclusion:
Gentamicin, at high concentrations, as achieved following topical application, inhibits cell proliferation in vitro and, therefore, may be detrimental to the repair process in vivo.
Insights
High concentrations of gentamicin used in bone infection treatment can harm osteoblast cells. This study shows gentamicin inhibits cell proliferation, potentially impairing bone healing.
Area of Science:
- Biochemistry
- Cell Biology
- Orthopedics
Background:
- Gentamicin is commonly used for bone infections.
- Local administration can achieve high drug concentrations.
- Potential toxicity to bone cells is a concern.
Purpose of the Study:
- To investigate the toxic effects of high gentamicin concentrations on human osteoblastlike cells.
- To assess the impact of gentamicin on cell proliferation and viability in vitro.
Main Methods:
- Human osteoblastlike cells were cultured.
- Cells were exposed to varying gentamicin concentrations (0-1000 microg/mL) for 4 days.
- Alkaline phosphatase activity, DNA content, and thymidine incorporation were measured.
Main Results:
- Gentamicin significantly decreased alkaline phosphatase activity starting at 100 microg/mL.
- Cell proliferation (thymidine incorporation) was reduced at concentrations of 100 microg/mL and above.
- Total DNA content decreased significantly at 700 microg/mL and higher.
Conclusions:
- High gentamicin concentrations inhibit osteoblast proliferation in vitro.
- Topical gentamicin may negatively affect bone repair processes in vivo.
- Further research is needed to optimize gentamicin use in bone infections.
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