Possible direct role of reactive oxygens in the cause of cutaneous phototoxicity induced by five quinolones in mice.
The mechanisms of phototoxicity induced in mice by five quinolone antibacterial agents were investigated using mouse 3T3 fibroblast cells and Balb/c mice. In the in vitro study, the cultured cells were exposed to ultraviolet-A (UVA) in the presence of the five quinolones lomefloxacin, enoxacin, ciprofloxacin, ofloxacin and DR-3355 (the s-isomer of ofloxacin). Cytotoxicity after irradiation was assayed by the neutral red and MTT assay methods, both of which revealed dose-dependent phototoxicity for all five quinolones. Phototoxicity was inhibited by the addition of catalase, and was augmented by the addition of superoxide dismutase. Dimethylthiourea (a hydroxyl radical scavenger) protected against phototoxicity induced by four quinolones, but not against that by enoxacin. These results indicated that superoxide anions, hydrogen peroxide and hydroxyl radicals were generated in solutions of these quinolones under UVA irradiation. In the in vivo study, mice were injected in the auricle with hydrogen peroxide. Ear swelling reactions appeared dose dependently. When irradiated, these reactions were significantly augmented. These data suggested that cutaneous phototoxicity in Balb/c mice is initiated by the generation of reactive oxygens in the target tissue, especially of hydroxyl radicals.
Wagai
N
N
Development Research Laboratories, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Tawara
K
K
D016475:3T3 Cells; D000818:Animals; D002374:Catalase / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D016166:Free Radical Scavengers; D005609:Free Radicals; D051379:Mice; D008807:Mice, Inbred BALB C; D010100:Oxygen / Q000378:metabolism*; D015363:Quinolones / Q000633:toxicity*; D012867:Skin / Q000187:drug effects* / Q000528:radiation effects; D013482:Superoxide Dismutase / Q000378:metabolism; D014466:Ultraviolet Rays
D016166:Free Radical Scavengers; D005609:Free Radicals; D015363:Quinolones; D002374:Catalase; D013482:Superoxide Dismutase; D010100:Oxygen