Possible reasons for differences in phototoxic potential of a 5 quinolone antibacterial agents: generation of toxic oxygen.
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.
Wagai
N
N
Developmental Research Laboratories, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Tawara
K
K
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000528:radiation effects / Q000633:toxicity*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004431:Ear, External; D004487:Edema / Q000139:chemically induced; D005260:Female; D005609:Free Radicals; D006861:Hydrogen Peroxide / Q000032:analysis; D008353:Mannitol / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D009603:Nitroso Compounds / Q000032:analysis; D010100:Oxygen / Q000633:toxicity*; D004369:Pentetic Acid / Q000494:pharmacology; D010777:Photochemistry; D015363:Quinolones / Q000737:chemistry / Q000528:radiation effects / Q000633:toxicity*; D013481:Superoxides / Q000032:analysis; D014466:Ultraviolet Rays
D000900:Anti-Bacterial Agents; D005609:Free Radicals; D009603:Nitroso Compounds; D015363:Quinolones; D013481:Superoxides; C008651:4-nitrosodimethylaniline; D008353:Mannitol; D004369:Pentetic Acid; D006861:Hydrogen Peroxide; D010100:Oxygen; D004121:Dimethyl Sulfoxide