PARTICIPATION OF REACTIVE OXYGEN SPECIES IN PHOTOTOXICITY INDUCED BY QUINOLONE ANTIBACTERIAL AGENTS

To elucidate the mechanism of phototoxicity induced as a side effect b y some of the new quinolone antibiotics, we studied sparfloxacin (SPFX ), lomefloxacin, enoxacin, ofloxacin, and ciprofloxacin, We first exam ined the photosensitized formation of reactive oxygen species such as singlet oxygen (O-1(2)) and superoxide anion (O-2(-)) mediated by the new quinolones, Al though a large number of studies have been reported , there is no direct evidence that these drugs generate reactive oxyge n species. We employed a near-infrared emission spectrometer to detect O-1(2)-specific emission (1268 nm), and the nitroblue tetrazolium red uction method to detect O-2(-). All the quinolones investigated in thi s study were found to produce O-1(2), Four drugs, but not SPFX, produc ed O-2(-). We also examined photodynamic DNA strand-breaking activity as a possible mechanism to explain the participation of reactive oxyge n species in the phototoxicity of the drugs. All the drugs exhibited p hotodynamic DNA strand-breaking activity. The inhibitory effect of sca vengers of reactive oxygen species indicated that the main active spec ies was O-1(2). The DNA strand-breaking activity was correlated not wi th the O-1(2)-forming ability, but with the affinity of the drugs for DNA, This result may be due to the short lifetime of O-1(2), These dat a suggested that the phototoxicity of the new quinolones was related t o DNA damage caused by reactive oxygen species, especially O-1(2). (C) 1997 Academic Press.