May 2005
Volume 46, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2005
Fluoroquinolone Eye Drop Cytotoxicity: Role of Preservatives in P2X Receptor Activation
Author Affiliations & Notes
  • P. Rat
    Cellular PharmacoToxicology,
    CHNO 15/20 – Hopital National Ophtalmologie, Paris, France
    Laboratoire de Toxicologie (INSERM U 598), Universite PARIS 5 – Faculte de Pharmacie, Paris, France
  • M. Dutot
    Cellular PharmacoToxicology,
    CHNO 15/20 – Hopital National Ophtalmologie, Paris, France
    Laboratoire de Toxicologie (INSERM U 598), Universite PARIS 5 – Faculte de Pharmacie, Paris, France
  • F. Pouzaud
    Cellular PharmacoToxicology,
    CHNO 15/20 – Hopital National Ophtalmologie, Paris, France
  • I. Larosche
    Cellular PharmacoToxicology,
    CHNO 15/20 – Hopital National Ophtalmologie, Paris, France
  • C. Baudouin
    Service 3,
    CHNO 15/20 – Hopital National Ophtalmologie, Paris, France
    Inserm u 598, Universite PARIS 5, Paris, France
  • J.–M. Warnet
    Cellular PharmacoToxicology,
    CHNO 15/20 – Hopital National Ophtalmologie, Paris, France
    Laboratoire de Toxicologie (INSERM U 598), Universite PARIS 5 – Faculte de Pharmacie, Paris, France
  • Footnotes
    Commercial Relationships  P. Rat, None; M. Dutot, None; F. Pouzaud, None; I. Larosche, None; C. Baudouin, None; J. Warnet, None.
  • Footnotes
    Support  Adebiopharm grant
Investigative Ophthalmology & Visual Science May 2005, Vol.46, 4891. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      P. Rat, M. Dutot, F. Pouzaud, I. Larosche, C. Baudouin, J.–M. Warnet; Fluoroquinolone Eye Drop Cytotoxicity: Role of Preservatives in P2X Receptor Activation . Invest. Ophthalmol. Vis. Sci. 2005;46(13):4891.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Abstract: : Purpose: Corneal perforations are observed after fluoroquinolone eye drop treatment. We investigated in vitro wether preservatives or fluoroquinolones used in ophthalmic solutions are implicated in ocular toxicity. Methods: Rabbit corneal cells was incubated with preserved (benzalkonium chloride, BAC) and unpreserved ofloxacin solutions for 15 minutes. Several concentrations of BAC were also tested (0.0025% to 0.01%). Membrane integrity, reactive oxygen species and superoxide anion productions were assessed using neutral red test, 2,7–dichlorofluorescin diacetate test and dihydroethidium test, respectively. P2X cell death receptor activation was evaluated using immunochemistry and chromatin condensation using Hoechst 33342 test. These tests were performed using cytofluorometry, adapted to microplate, and inverted fluorescence microscopy. Results: A significant decrease of membrane integrity was observed with the preserved solution, not with the unpreserved solution; all the BAC concentrations induce a decrease too. Reactive oxygen species production and superoxide anion production were observed with every solution but the production was higher with the preserved solution and the BAC solutions. The preserved solution and the BAC solution at the same concentration induced apoptosis with P2X receptor activation, whereas the unpreserved solution did not. DISCUSSION: Cytotoxicity observed with fluoroquinolone eye drops seems to be mainly due to preservatives wich induce oxidative stress associated with apoptosis. Quaternary ammoniums have already been incriminated in antiglaucomatous long term treatment intolerance. Corneal acute toxicity seems to be associated to P2X cell death receptor activation Conclusions: It should be preferable to use new fluoroquinolone generation eye drop (moxifloxacin, levofloxacin) in free–preservative formulations.

Keywords: drug toxicity/drug effects • apoptosis/cell death • oxidation/oxidative or free radical damage 
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×