STIMULATION OF PROSTAGLANDIN PRODUCTION BY QUINOLONE PHOTOTOXICITY INBALB C 3T3 MOUSE FIBROBLAST CELLS IN-VITRO/

Sparfloxacin (SPFX) and levofloxacin (LVFX) with ultraviolet-A (UVA) i rradiation have been reported to induce skin inflammation due to photo toxicity in Balb/c mice. We examined the production of arachidonic aci d metabolites induced by quinolone phototoxicity in Balb/c 3T3 mouse f ibroblast cells in vitro. The cells were simultaneously treated with S PFX or LVFX at 1, 10, or 100 mu M and UVA irradiation for 5 min (0.5 J /cm(2)). They were then cultured in quinolone-free medium for 24 hr, a nd the concentrations of prostaglandin E-2 (PGE(2)), 6-ketoprostagland in F-1 alpha (6-keto-PGF(1 alpha)), and leukotriene B-4 (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 PGE(2) level were also examined. Treatment with SP FX at 100 mu M plus UVA irradiation markedly increased levels of PGE(2 ) and 6-keto-PGF(1 alpha), but not that of LTB4. SPFX or LVFX alone at up to 100 mu M, 10 mu M SPFX, or 100 mu M LVFX, Or less plus UVA irra diation, or UVA-preirradiated quinolone up to 100 mu M had no effect. Indomethacin even at 0.1 mu M completely inhibited the PGE(2) elevatio n induced by 100 mu M SPFX with UVA. These results suggest that PGs re leased from dermal fibroblasts in the simultaneous presence of quinolo ne and UVA could contribute in part to the development of skin inflamm ation in vivo. (C) 1997 Society of Toxicology.