Possible reasons for differences in phototoxic potential of a 5 quinolone antibacterial agents: generation of toxic oxygen

Free Radic Res Commun. 1992;17(6):387-98. doi: 10.3109/10715769209083143.

Abstract

The reason for the differences in phototoxic potential between the 5 quinolone antibacterial agents lomefloxacin, enoxacin, ciprofloxacin, ofloxacin and DR-3355 (the s-isomer of ofloxacin) in mice was investigated. Superoxide anion, hydrogen peroxide (H2O2), and bleaching of p-nitrosodimethylaniline (B-NDMA) were detected in quinolone solutions during irradiation with ultraviolet-A (UVA). Apparent levels of H2O2 and the B-NDMA per mole of quinolone paralled the phototoxic potentials in the mice. The N-NDMA induced by quinolones and UVA was inhibited partially by treatment with D-mannitol and dimethylsulfoxide, and also with diethylenetriamine-pentaaceticacid (DTPA), suggesting that Haber-Weiss and Fenton reactions occurred. UVA concentration-dependently increased the level of the B-NMDA in H2O2 solution and the swelling in the ear pretreated by intra-auricular injection of H2O2. Both augmentations were inhibited by DTPA or DMSO. The swelling induced by the 5 quinolones and UVA was completely inhibited by pretreatment with dimethylsulfoxide. Oxygen consumption was detectable during the photodegradation, and increased with time. These results showed that the phototoxic potentials of the 5 quinolones were probably related to the amounts of toxic oxygens generated in the target cells during irradiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / radiation effects
  • Anti-Bacterial Agents / toxicity*
  • Dimethyl Sulfoxide / pharmacology
  • Ear, External
  • Edema / chemically induced
  • Female
  • Free Radicals
  • Hydrogen Peroxide / analysis
  • Mannitol / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • Molecular Structure
  • Nitroso Compounds / analysis
  • Oxygen / toxicity*
  • Pentetic Acid / pharmacology
  • Photochemistry
  • Quinolones / chemistry
  • Quinolones / radiation effects
  • Quinolones / toxicity*
  • Superoxides / analysis
  • Ultraviolet Rays

Substances

  • Anti-Bacterial Agents
  • Free Radicals
  • Nitroso Compounds
  • Quinolones
  • Superoxides
  • 4-nitrosodimethylaniline
  • Mannitol
  • Pentetic Acid
  • Hydrogen Peroxide
  • Oxygen
  • Dimethyl Sulfoxide