Impairment of phagocytic cell respiratory burst by UVA in the presence of fluoroquinolones: an oxygen-dependent phototoxic damage to cell surface microvilli.
Fluoroquinolones are widely used clinically as broad-spectrum antimicrobial agents. One of their side effects is UVA-dependent photosensitivity, observed after the skin is exposed to sunlight. We have investigated five fluoroquinolones and have found that their phototoxicity is oxygen dependent. Human phagocytic leucocytes were stimulated with serum opsonized zymosan to produce superoxide radical (O2-) (respiratory burst) in the presence of a sensitive O2(-)-specific cypridina luciferin analogue, 2-methyl-6-(p-methoxyphenyl)-3,7-dihydroimidazol (1,2-alpha) pyrazin-one hydrochloride (MCLA), as chemiluminescence reagent with which O2- can react to induce photon emission. The photon count was used as a measure of respiratory burst activity. When leucocytes were irradiated with UVA for 10 min in the presence of 3 micrograms ml-1 lomefloxacin, ciprofloxacin or norfloxacin, a marked decrease in respiratory burst activity was observed; in this respect, ofloxacin and tosufloxacin were weak. Scanning electron microscopy revealed that the cell surface microvilli were destroyed. The phototoxicity of fluoroquinolones could be abolished if oxygen in the tests was replaced by nitrogen or if the aminothiol DL-cysteine (1.5 mg ml-1) was added prior to irradiation. It is suggested that an oxygen species derived from UVA-excited drug molecules and oxygen mediates the phototoxicity of these fluoroquinolones.
Saniabadi
A R
AR
Japan Immunoresearch Laboratories, Takasaki, Japan.
Wada
K
K
Umemura
K
K
Sakuma
S
S
Nakashima
M
M
D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D024841:Fluoroquinolones; D006801:Humans; D066298:In Vitro Techniques; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D015394:Molecular Structure; D010100:Oxygen / Q000378:metabolism; D010586:Phagocytes / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D016897:Respiratory Burst / Q000528:radiation effects*; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D014466:Ultraviolet Rays; D015054:Zymosan / Q000494:pharmacology
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D013481:Superoxides; D015054:Zymosan; D010100:Oxygen