Damage to mitochondria of cultured human skin fibroblasts photosensitized by fluoroquinolones

The phototoxic fluoroquinolones ofloxacin, lomefloxacin, norfloxacin, cipro floxacin and BAYy 3118 have ionizable groups with pK(a) values close to neu trality. Different ionic species of these fluoroquinolones, therefore, part ition in various compartments and organelles of living cells according to t heir ionic equilibria. While all these fluoroquinolones accumulate in lysos omes, they more or less stain the rest of the cytoplasm of Living HS 68 fib roblasts. As a result, photosensitized damage to other cytoplasmic sites th an lysosomes can also be expected. Using microfluorometry and rhodamine 123 (Rh 123) as a specific fluorescent probe which is released from mitochondr ia by light absorption, we show that under ultraviolet A (UVA) irradiation norfloxacin and ciprofloxacin readily damage mitochondrial membranes, as ev idenced by the UVA dose-dependent strongly accelerated release of Rh 123 fr om mitochondria in cells treated with norfloxacin and ciprofloxacin. Damage s are already noticeable at WA doses as low as 2 J/cm(2). By contrast, no s uch photoinduced damage can be observed with ofloxacin, lomefloxacin and BA Yy 3118, the latter bring the most phototoxic derivative towards HS 68 fibr oblasts. The initial photodamage induced by norfloxacin and ciprofloxacin c an then propagate after the irradiation as shown by the strongly increased rate of release of Rh 123 from mitochondria of cells that have been incubat ed with these two fluoroquinolones and left in the dark after a pre-irradia tion with 18 J/cm(2) of UVA. Interestingly, the same pre-irradiation after cells have been treated with BAYS 3118 and lomefloxacin induces similar pos t-irradiation effects, although they have no apparent immediate photosensit izing action on mitochondria. (C) 2000 Elsevier Science B.V. All rights res erved.