Detection and prevention of ocular phototoxicity of ciprofloxacin and other fluoroquinolone antibiotics.
Fluoroquinolone (FLQ) drugs are a potent family of antibiotics used to treat infections including ocular infections. To determine if these antibiotics may be phototoxic to the eye, we exposed human lens epithelial cells to 0.125-1 mm FLQs (ciprofloxacin [Cipro], lomefloxacin [Lome], norfloxacin [Nor] and ofloxacin [Ofl]), the precursor quinolone nalidixic acid (Nalid) and UVA radiation (2.5 J cm(-2)). Based on fluorescence confocal microscopy, FLQs are diffused throughout the cytoplasm and preferentially located in the lysosomes of lens epithelial cells. Neither FLQ exposure alone nor UVA exposure alone reduced cell viability. However, with exposure to UVA radiation the FLQs studied (Cipro, Nor, Lome and Ofl) induced a phototoxic reaction that included necrosis, apoptosis, loss of cell viability as measured by MTS, and membrane damage as determined by the lactate dehydrogenase assay. Both Nalid and all FLQs studied (Cipro, Nor, Lome and Ofl) photopolymerized the lens protein alpha-crystallin. Phototoxic damage to lens epithelial cells and/or alpha-crystallin will lead to a loss of transparency of the human lens. However, if precautions are taken to filter all UV radiation from the eye while taking these antibiotics, eye damage may be prevented.
Laboratory of Toxicology and Pharmacology, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA.
Baozhong
B
Zhao
Colin F
CF
Chignell
Mustapha
M
Rammal
Frank
F
Smith
Mary G
MG
Hamilton
Usha P
UP
Andley
Joan E
JE
Roberts
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D002939:Ciprofloxacin / Q000737:chemistry / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects* / Q000528:radiation effects; D024841:Fluoroquinolones / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007908:Lens, Crystalline / Q000166:cytology* / Q000187:drug effects / Q000528:radiation effects; D015394:Molecular Structure; D010777:Photochemistry; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D014466:Ultraviolet Rays
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D017319:Photosensitizing Agents; D002939:Ciprofloxacin