title: Intrinsic cytotoxic effects of fluoroquinolones on human corneal keratocytes and endothelial cells.
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).
  
  
  METHODS
  Cultures of replicating HCK and HCE were exposed to ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin, or ofloxacin concentrations of 1 mg/mL, 100 microg/mL, 10 microg/mL, 1 microg/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.
  
  
  METHODS
  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.
authors.affiliation: Santen Incorporated, Napa, CA 94558, USA. pbezwada@santeninc.com
authors.forename: Padma
authors.initials: P
authors.lastname: Bezwada
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Clark
authors.forename: Susan
authors.initials: S
authors.lastname: Schneider
mesh_terms: D000900:Anti-Bacterial Agents / Q000633:toxicity*; D001372:Aza Compounds / Q000633:toxicity; D001681:Biological Assay; D002939:Ciprofloxacin / Q000633:toxicity; D003315:Cornea / Q000166:cytology / Q000187:drug effects*; D003319:Corneal Stroma / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects; D004728:Endothelium, Corneal / Q000187:drug effects*; D024841:Fluoroquinolones / Q000633:toxicity*; D000077734:Gatifloxacin; D006801:Humans; D066298:In Vitro Techniques; D064704:Levofloxacin; D000077266:Moxifloxacin; D015242:Ofloxacin / Q000633:toxicity; D011804:Quinolines / Q000633:toxicity
chemical_list: D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D002939:Ciprofloxacin; D064704:Levofloxacin; D015242:Ofloxacin; D000077734:Gatifloxacin; D000077266:Moxifloxacin