Photosensitizing mechanism and identification of levofloxacin photoproducts at ambient UV radiation

Photochem Photobiol. 2012 Mar-Apr;88(2):344-55. doi: 10.1111/j.1751-1097.2011.01068.x. Epub 2012 Jan 25.

Abstract

Levofloxacin (LVFX) is a broad spectrum third generation fluoroquinolone antibiotic, used in the treatment of severe or life-threatening bacterial infections. Photosensitizing mechanism of LVFX was investigated under the ambient environmental intensities of UV-A, UV-B and sunlight exposure. Phototoxic effects of LVFX were assessed on NIH-3T3 and HaCaT cell lines. Results identified first time three photoproducts of LVFX at ambient levels of UV-R by LC-MS/MS. The generation of reactive oxygen species (ROS) was investigated photochemically as well as intracellularly in HaCaT cell line. ROS were significantly quenched by specific quenchers like DABCO, NaN(3), D-mannitol and NAC. Photosensitized LVFX caused lipid peroxidation at different concentrations. Quenching study with superoxide dismutase confirms the LVFX-induced lipid photoperoxidation. Further, photocytotoxicity of LVFX showed significant reduction in cell viability by MTT and neutral red uptake assays. LVFX caused cell arrest in G2/M phases as well as induced apoptosis through ROS-dependent pathway. In addition, photosensitized LVFX also induced upregulation of p21 and Bax/Bcl-2 genes ratio. India is a tropical country and most of the human activities such as agriculture, commerce, sports, etc. take place in bright sunlight; therefore, photosensitive LVFX may lead to skin/ocular disorders and immune suppression. Information is needed regarding the phototoxicity of LVFX for human safety.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Cycle Checkpoints / drug effects*
  • Cell Line
  • Cell Survival / drug effects
  • Fibroblasts / drug effects*
  • Fibroblasts / radiation effects
  • Free Radical Scavengers / pharmacology
  • Humans
  • Keratinocytes / drug effects*
  • Keratinocytes / radiation effects
  • Levofloxacin*
  • Lipid Peroxidation / drug effects
  • Mice
  • Ofloxacin* / adverse effects
  • Ofloxacin* / chemistry
  • Ofloxacin* / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Reactive Oxygen Species / antagonists & inhibitors
  • Reactive Oxygen Species / metabolism
  • Sunlight
  • Superoxide Dismutase / antagonists & inhibitors
  • Superoxide Dismutase / metabolism
  • Ultraviolet Rays
  • Up-Regulation
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism
  • p21-Activated Kinases / genetics
  • p21-Activated Kinases / metabolism

Substances

  • Free Radical Scavengers
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • bcl-2-Associated X Protein
  • Levofloxacin
  • Ofloxacin
  • Superoxide Dismutase
  • p21-Activated Kinases