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 antimicr obial agents. One of their side effects is UVA-dependent photosensitiv ity, observed after the skin is exposed to sunlight. We have investiga ted five fluoroquinolones and have found that their phototoxicity is o xygen dependent. Human phagocytic leucocytes were stimulated with seru m opsonized zymosan to produce superoxide radical (O-2(-)) (respirator y burst) in the presence of a sensitive O-2(-)-specific cypridina luci ferin analogue, 6-(p-methoxyphenyl)-3,7-dihydroimidazol(1,2-alpha) pyr azin-one hydrochloride (MCLA), as chemiluminescence reagent with which O-2(-) can react to induce photon emission. The photon count was used as a measure of respiratory burst activity. When leucocytes were irra diated with UVA for 10 min in the presence of 3 mu g ml(-1) lomefloxac in, ciprofloxacin or norfloxacin, a marked decrease in respiratory bur st 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 coul d be abolished if oxygen in the tests was replaced by nitrogen or if t he aminothiol DL-cysteine (1.5 mg ml(-1)) was added prior to irradiati on. It is suggested that an oxygen species derived from UVA-excited dr ug molecules and oxygen mediates the phototoxicity of these fluoroquin olones.