IngentaConnect Intrinsic cytotoxic effects of fluoroquinolones on human corneal ...

Abstract:

Objective: To determine the intrinsic cytotoxicity of five fluoroquinolones (ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin, ofloxacin) on human corneal keratocytes (HCK) and human corneal endothelial cells (HCE).

Research design and methods: Cultures of replicating HCK and HCE were exposed to ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin, or ofloxacin concentrations of 1 mg/mL, 100 μg/mL, 10 μg/mL, 1 μg/mL, 100 ng/mL, or 10 ng/mL for 15, 30, 60, or 240 min. Each of the 24 fluoroquinolone concentration-time exposures was tested against its own serum-free minimal essential medium (MEM) control. Cell number was quantified with a fluorescence bioassay.

Main outcome measure: Cytotoxicity was defined as a significant (p < 0.05) difference in cell number measured as mean calcein fluorescence product versus control for each fluoroquinolone concentration-time exposure.

Results: Fluoroquinolone-induced cytotoxicity was concentration- and time-dependent in HCK and HCE cultures. The number of cytotoxic concentration-time exposures was highest with ciprofloxacin (23 of 24 exposures in HCK and 24 of 24 exposures in HCE) and lowest with levofloxacin (10 of 24 exposures in both HCK and HCE).

Conclusions: In vitro cell cultures are useful for evaluating cell response to potentially toxic insults, although cell cultures may lack tissue components that may prevent or ameliorate damage in vivo. In this assay, fluoroquinolones displayed the potential to be cytotoxic to human corneal keratocytes and endothelial cells, depending on drug concentration and duration of exposure. The potential for cytotoxicity may differ among fluoroquinolones.

Keywords: CORNEA; CYTOTOXICITY; FLUOROQUINOLONES; KERATOCYTES

Document Type: Research article

DOI: 10.1185/030079908X261005

Affiliations: 1: Santen Incorporated, Napa, CA, USA

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Intrinsic cytotoxic effects of fluoroquinolones on human corneal keratocytes and endothelial cells