Stimulation of prostaglandin production by quinolone phototoxicity in Balb/c 3T3 mouse fibroblast cells in vitro.
Sparfloxacin (SPFX) and levofloxacin (LVFX) with ultraviolet-A (UVA) irradiation have been reported to induce skin inflammation due to phototoxicity in Balb/c mice. We examined the production of arachidonic acid metabolites induced by quinolone phototoxicity in Balb/c 3T3 mouse fibroblast cells in vitro. The cells were simultaneously treated with SPFX or LVFX at 1, 10, or 100 microM and UVA irradiation for 5 min (0.5 J/cm2). They were then cultured in quinolone-free medium for 24 hr, and the concentrations of prostaglandin E2 (PGE2), 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), and leukotriene B4 (LTB4) in the incubation medium were measured. Furthermore, the effect of quinolone photoproducts on the production of the inflammatory mediators and that of indomethacin on PGE2 level were also examined. Treatment with SPFX at 100 microM plus UVA irradiation markedly increased levels of PGE2 and 6-keto-PGF1 alpha, but not that of LTB4. SPFX or LVFX alone at up to 100 microM, 10 microM SPFX, or 100 microM LVFX, or less plus UVA irradiation, or UVA-preirradiated quinolone up to 100 microM had no effect. Indomethacin even at 0.1 microM completely inhibited the PGE2 elevation induced by 100 microM SPFX with UVA. These results suggest that PGs released from dermal fibroblasts in the simultaneous presence of quinolone and UVA could contribute in part to the development of skin inflammation in vivo.
Shimoda
K
K
Drug Safety Research Laboratory, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Wagai
N
N
Kato
M
M
D016475:3T3 Cells; D042462:4-Quinolones; D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D000890:Anti-Infective Agents / Q000633:toxicity*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D017484:Dermatitis, Phototoxic / Q000378:metabolism*; D015232:Dinoprostone / Q000096:biosynthesis; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000096:biosynthesis; D007975:Leukotriene B4 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis*; D014466:Ultraviolet Rays
D042462:4-Quinolones; D000890:Anti-Infective Agents; D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D007975:Leukotriene B4; D015121:6-Ketoprostaglandin F1 alpha; D007770:L-Lactate Dehydrogenase; D015232:Dinoprostone; D007213:Indomethacin