Analyses of cutaneous fluoroquinolones photoreactivity using the integrated model for the differentiation of skin reactions.
Currently available test models for the differentiation of photoallergic and photoirritant reactions are extremely time consuming and the protocols are very heterogeneous. In vitro tests are of proven value in predicting irritant or toxic effects, but these tests fail to predict chemical-induced allergic side effects. We developed test systems for this endpoint which is not easily detected by existing assays. In a previous publication we were able to discriminate between a contact sensitizer and a skin irritant with a combination of primary ear swelling analysis and cell counting of the ear-draining lymph nodes [Toxicol. Appl. Pharm. 153 (1998) 83; Arch. Toxicol. 73 (2000) 501]. This combination of tests was called the Integrated Model for the Differentiation of chemical-induced allergic and irritant Skin reactions (IMDS). In addition, it had been shown before that inclusion of UV irradiation in the local lymph node assay enables discrimination of photoallergic from photoirritant reactions after dermal application [Photodermatol. Photoimmunol. Photomed. 10 (1994) 57]. Because of the fact that fluoroquinolones are known to induce photoreactions after oral but not dermal treatment, the aim of the present study was to apply the IMDS for the fast and reliable differentiation of photoreactions due to fluoroquinolones after oral treatment. Enoxacin, lomefloxacin, ofloxacin, sparfloxacin and BAY y 3118 were tested in this system. We found a good correlation between the results of UV light-irradiated IMDS and a guinea pig model with the quinolones as far as photoirritancy was concerned. This holds true also for the photoallergic standard olaquindox and the photoirritant standard 8-methoxypsoralen. However, in contrast to the guinea pig assays the IMDS is fast and extremely predictive for the risk of both photosensitization and photoirritancy depending on the route of exposure. Thus, the UV light-irradiated IMDS turned out to be a good tool for the preclinical risk assessment procedure in terms of discriminating photoreactions. In addition, flow cytometric analyses were used to underline the fact that antigen-independent activation occurred after the induction of photoirritant reactions.
Blotz
A
A
Institute of Toxicology, Bayer AG, Wuppertal, Germany.
Michel
L
L
Moysan
A
A
Blümel
J
J
Dubertret
L
L
Ahr
H J
HJ
Vohr
H W
HW
D000284:Administration, Oral; D000287:Administration, Topical; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D015415:Biomarkers; D002462:Cell Membrane / Q000378:metabolism; D015365:Enoxacin / Q000494:pharmacology; D005260:Female; D024841:Fluoroquinolones; D007509:Irritants / Q000494:pharmacology; D051379:Mice; D008954:Models, Biological; D015242:Ofloxacin / Q000494:pharmacology; D010641:Phenotype; D017319:Photosensitizing Agents / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects
D000890:Anti-Infective Agents; D015415:Biomarkers; D024841:Fluoroquinolones; D007509:Irritants; D017319:Photosensitizing Agents; D015363:Quinolones; C079807:Bay Y3118; D015365:Enoxacin; D015242:Ofloxacin; C053091:lomefloxacin; C061363:sparfloxacin