Apoptotic photoreceptor cell death induced by quinolone phototoxicity in mice

• Published in: Toxicology letters Vol. 105; no. 1; pp. 9 - 15
• Main Authors: Shimoda, Kohji, Kato, Michiyuki
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 08.03.1999; Amsterdam Elsevier Science
• Subjects: 4-Quinolones; Animals; Anti-Infective Agents - toxicity; Apoptosis; Apoptosis - drug effects; Apoptosis - radiation effects; Biological and medical sciences; Chromosomes - drug effects; Chromosomes - radiation effects; Chromosomes - ultrastructure; DNA Fragmentation; Drug toxicity and drugs side effects treatment; Female; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Inbred DBA; Microscopy, Electron; Mouse; Pharmacology. Drug treatments; Photoreceptor Cells, Vertebrate - cytology; Photoreceptor Cells, Vertebrate - drug effects; Photoreceptor Cells, Vertebrate - radiation effects; Photoreceptor Cells, Vertebrate - ultrastructure; Phototoxicity; Quinolone; Retina; Species Specificity; Toxicity: eye; Ultraviolet Rays; Phototoxicity; Retina; Quinolone; Mouse; Apoptosis; UVA radiation; Pigmentation disorder; Albinism; Toxicity; Rodentia; Single dose; Photoreceptor; Oral administration; Ingestion; Vertebrata; Fluoroquinolone derivatives; Eye disease; Mammalia; Cell death; Animal; Antibacterial agent; Quinolone derivatives
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/S0378-4274(98)00378-6

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/cm 2 for 4 h (21.6 J/cm 2). 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.