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Endothelial cell compatibility of fluoroquinolone solutions for intravenous use
H Vorbach1, G Weigel, B Robibaro
1Department of Infectious Diseases, University Hospital of Vienna, Austria.
Abstract:
One local side-effect closely related to the use of parenteral fluoroquinolones is phlebitis. The occurrence of this phenomenon is largely thought due to the damage of endothelial cells with subsequent inflammation. In order to evaluate the effect of ciprofloxacin, fleroxacin, and ofloxacin on the viability of human umbilical venous endothelial cells (HUVEC), intracellular ATP levels were measured by a luciferin-luciferase assay. Prostacyclin (PGI2) and thromboxane A2 (TXA2) were determined by means of direct radioimmunoassay. Commercially available preparations of ciprofloxacin (2 mg/ml) and fleroxacin (4 mg/ml) reduced the intracellular ATP content by 75.9 +/- 1.9% and 82.1 +/- 0.6%, respectively, within 20 minutes, indicating severe damage of endothelial cells. Incubation with ofloxacin (2 mg/ml) did not have any detrimental effect. All fluoroquinolones were tolerated well by endothelial cells at low concentrations up to 20 micrograms/ml. Concentrations between 100-200 micrograms/ml gradually led to functional alterations such as increased PGI2 release. The tolerance of intravenously applied antibiotics has been tested in animal models. Use of human venous endothelial cells for testing antibiotic solutions for intravenous application provides a valuable alternate model for tolerability.
Insights
Parenteral fluoroquinolones like ciprofloxacin and fleroxacin severely damage endothelial cells, increasing phlebitis risk. Ofloxacin showed no adverse effects on these cells, suggesting it may be a safer alternative.
Area of Science:
- Vascular Biology
- Pharmacology
- Cell Biology
Background:
- Phlebitis is a common side effect of parenteral fluoroquinolones.
- Endothelial cell damage and inflammation are believed to cause phlebitis.
Purpose of the Study:
- To assess the impact of ciprofloxacin, fleroxacin, and ofloxacin on human umbilical venous endothelial cell (HUVEC) viability.
- To evaluate the potential of HUVECs as an in vitro model for assessing intravenous antibiotic tolerability.
Main Methods:
- Intracellular ATP levels in HUVECs were measured using a luciferin-luciferase assay to determine cell viability.
- Prostacyclin (PGI2) and thromboxane A2 (TXA2) levels were quantified via direct radioimmunoassay.
- HUVECs were incubated with varying concentrations of ciprofloxacin, fleroxacin, and ofloxacin.
Main Results:
- Ciprofloxacin (2 mg/ml) and fleroxacin (4 mg/ml) significantly reduced intracellular ATP levels by over 75% within 20 minutes, indicating severe endothelial cell damage.
- Ofloxacin (2 mg/ml) did not cause significant detrimental effects on HUVEC viability.
- At concentrations up to 20 µg/ml, all tested fluoroquinolones were well-tolerated. Higher concentrations (100-200 µg/ml) led to functional alterations, including increased PGI2 release.
Conclusions:
- Ciprofloxacin and fleroxacin exhibit significant cytotoxicity to HUVECs, potentially explaining their association with phlebitis.
- Ofloxacin demonstrates better tolerability in HUVECs compared to ciprofloxacin and fleroxacin.
- Human venous endothelial cells provide a valuable in vitro model for evaluating the tolerability of intravenously administered antibiotics.