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Participation of reactive oxygen species in phototoxicity induced by quinolone antibacterial agents
Abstract:
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 (O2-) 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 detect 1O2-specific emission (1268 nm), and the nitroblue tetrazolium reduction method to detect O2-. All the quinolones investigated in this study were found to produce 1O2. Four drugs, but not SPFX, produced O2-. 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 was 1O2. The DNA strand-breaking activity was correlated not with the 1O2-forming ability, but with the affinity of the drugs for DNA. This result may be due to the short lifetime of 1O2. These data suggested that the phototoxicity of the new quinolones was related to DNA damage caused by reactive oxygen species, especially 1O2.
Insights
New quinolone antibiotics can cause phototoxicity by generating reactive oxygen species, particularly singlet oxygen (1O2). This study links this phototoxicity to DNA damage mediated by these reactive oxygen species.
Area of Science:
- Pharmacology
- Photobiology
- Molecular Biology
Background:
- New quinolone antibiotics can cause phototoxicity.
- The precise mechanism of this side effect remains unclear.
- Reactive oxygen species (ROS) are implicated in phototoxicity.
Purpose of the Study:
- To investigate the mechanism of phototoxicity induced by new quinolone antibiotics.
- To determine if these drugs generate reactive oxygen species (ROS) like singlet oxygen (1O2) and superoxide anion (O2-).
- To assess the role of ROS in photodynamic DNA strand-breaking activity.
Main Methods:
- Studied five quinolone antibiotics: sparfloxacin, lomefloxacin, enoxacin, ofloxacin, and ciprofloxacin.
- Used near-infrared emission spectrometry to detect singlet oxygen (1O2).
- Employed the nitroblue tetrazolium reduction method to detect superoxide anion (O2-).
- Assessed photodynamic DNA strand-breaking activity and the effect of ROS scavengers.
Main Results:
- All investigated quinolones produced singlet oxygen (1O2).
- Four of the five quinolones produced superoxide anion (O2-).
- All drugs exhibited photodynamic DNA strand-breaking activity, primarily mediated by singlet oxygen (1O2).
- DNA strand-breaking activity correlated with drug-DNA affinity, not 1O2 production, likely due to 1O2's short lifetime.
Conclusions:
- Phototoxicity of new quinolone antibiotics is linked to DNA damage.
- Reactive oxygen species, especially singlet oxygen (1O2), play a key role in this DNA damage.
- The findings provide insight into the mechanism of quinolone-induced phototoxicity.