Participation of Reactive Oxygen Species in Phototoxicity Induced by Quinolone Antibacterial Agents

To elucidate the mechanism of phototoxicity induced as a side effect by some of the new quinolone antibiotics, we studied sparfloxacin (SPFX), lomefloxacin, enoxacin, ofloxacin, and ciprofloxacin. We first examined the photosensitized formation of reactive oxygen species such as singlet oxygen (1O2) and superoxide anion (O−2) mediated by the new quinolones. Although a large number of studies have been reported, there is no direct evidence that these drugs generate reactive oxygen species. We employed a near-infrared emission spectrometer to detect1O2-specific emission (1268 nm), and the nitroblue tetrazolium reduction method to detect O−2. All the quinolones investigated in this study were found to produce1O2. Four drugs, but not SPFX, produced O−2. We also examined photodynamic DNA strand-breaking activity as a possible mechanism to explain the participation of reactive oxygen species in the phototoxicity of the drugs. All the drugs exhibited photodynamic DNA strand-breaking activity. The inhibitory effect of scavengers of reactive oxygen species indicated that the main active species was1O2. The DNA strand-breaking activity was correlated not with the1O2-forming ability, but with the affinity of the drugs for DNA. This result may be due to the short lifetime of1O2. These data suggested that the phototoxicity of the new quinolones was related to DNA damage caused by reactive oxygen species, especially1O2.