Apoptotic photoreceptor cell death induced by quinolone phototoxicity in mice.
We examined retinal degeneration induced by phototoxicity of quinolone antibacterial agents. Albino Balb/c and pigmented DBA/2 mice fasted overnight were given a single oral administration of ciprofloxacin (CPFX), levofloxacin (LVFX), enoxacin (ENX), lomefloxacin (LFLX) or sparfloxacin (SPFX), followed by ultraviolet-A (UVA) irradiation at 1.5 mW/cm2 for 4 h (21.6 J/cm2). At 24 h after quinolone administration, the mice were sacrificed, and the eyes were then histologically examined. ENX or LFLX at 200 or 400 mg/kg or SPFX at 50 or 100 mg/kg plus UVA induced retinal degeneration in Balb/c mice, whereas no histological change was observed in the eyes of DBA/2 mice. CPFX and LVFX at 800 mg/kg plus UVA had no effect on the eyes in either Balb/c or DBA/2 mice. Agarose gel electrophoresis showed that chromosomal DNA extracted from the eyes of Balb/c mice was fragmented in the SPFX 100 mg/kg group, but not in the LVFX 800 mg/kg group. In the electron microscopic examination, swelling of mitochondria and disruption of the cytoplasm were observed in the photoreceptor inner segment (PIS) at 2 h, and disarrangement of lamellar disks in the outer segment (POS) and condensed chromatin in photoreceptor cell nuclei in the outer nuclear layer (ONL) were observed at 4 h after 100 mg/kg SPFX administration to Balb/c mice. These results suggest that quinolone plus UVA irradiation induces retinal degeneration in albino Balb/c mice, but not in DBA/2 mice, and this degeneration is associated with apoptotic photoreceptor cell death.
Shimoda
K
K
Drug Safety Research Laboratory, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan. shimoz8j@daiichipharm.co.jp
Kato
M
M
D042462:4-Quinolones; D000818:Animals; D000890:Anti-Infective Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002875:Chromosomes / Q000187:drug effects / Q000528:radiation effects / Q000648:ultrastructure; D053938:DNA Fragmentation; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008854:Microscopy, Electron; D020419:Photoreceptor Cells, Vertebrate / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects* / Q000648:ultrastructure; D013045:Species Specificity; D014466:Ultraviolet Rays
D042462:4-Quinolones; D000890:Anti-Infective Agents