© 1997 Oxford University Press
research-article |
Stimulation of Prostaglandin Production by Quinolone Phototoxicity in Balb/c 3T3 Mouse Fibroblast Cells in Vitro
Drug Safety Research Laboratory, Daiichi Pharmaceutical Co., Ltd. 1-16-13, Kita-Kasai, Edogawa-ku, Tokyo 134, Japan
Received August 30, 1996; accepted December 27, 1996
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 µM 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
(6-keto-PGF1), 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 µM plus UVA irradiation markedly increased levels of PGE2 and 6-keto-PGF1 but not that of LTB SPFX or LVFX alone at up to 100 µM, 100 µM SPFX, or 100µM LVFX, or less plus UVA irradiation, or UVA-preirradiated quinolone up to 100µM had no effect. indomethacin even at 0.1 µM completely inhibited the PGE2 elevation induced by 100 µM 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.