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, cipr...

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Bibliographic Details
Published in:Archives of toxicology 1992-07, Vol.66 (6), p.392-397
Main Authors: WAGAI, N, TAWARA, K
Format: Article
Language:English
Subjects:
3T3 Cells
Animals
Biological and medical sciences
Catalase - metabolism
Cell Survival - drug effects
Cell Survival - radiation effects
Drug toxicity and drugs side effects treatment
Free Radical Scavengers
Free Radicals
Medical sciences
Mice
Mice, Inbred BALB C
Miscellaneous (drug allergy, mutagens, teratogens...)
Oxygen - metabolism
Pharmacology. Drug treatments
Quinolones - toxicity
Skin - drug effects
Skin - radiation effects
Superoxide Dismutase - metabolism
Ultraviolet Rays
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Summary: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.
ISSN:0340-5761
1432-0738
DOI:10.1007/bf02035128