Lysosomes are sites of fluoroquinolone photosensitization in human skin fibroblasts: a microspectrofluorometric approach.
The fluoroquinolone antibiotics are widely used despite their strong phototoxicity under solar UV irradiation. Although they are known as good photodynamic photosensitizers, other factors than production of activated oxygen species may play a role in the effectiveness of the phototoxic effect. Subcellular localization is one of the important parameters that may determine this strength. Using microspectrofluorometry, it is shown that norfloxacin, ofloxacin, lomefloxacin, ciproflaxin and BAYy3118 are readily incorporated into lysosomes of HS68 human skin fibroblasts although weak staining of the whole cytoplasm also occurs especially with norfloxacin. Consistent with their photoinstability in solutions, the fluoroquinolones under study are readily photobleached by UVA in the HS68 fibroblasts. The BAYy3118 derivative that has the fastest bleaching rate also shows the strongest phototoxicity toward HS68 fibroblasts. Photosensitization with these fluoroquinolones induces lysosomal membrane damage as shown by the increased rate of leakage of the lysosomal probe lucifer yellow as compared to that observed with untreated cells.
Ouedraogo
G
G
Muséum National d'Histoire Naturelle, Laboratoire de Photobiologie, Paris, France.
Morlière
P
P
Bazin
M
M
Santus
R
R
Kratzer
B
B
Miranda
M A
MA
Castell
J V
JV
D000890:Anti-Infective Agents / Q000378:metabolism / Q000633:toxicity*; D002460:Cell Line; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005456:Fluorescent Dyes; D024841:Fluoroquinolones; D006801:Humans; D008247:Lysosomes / Q000187:drug effects* / Q000378:metabolism; D018462:Photobiology; D017319:Photosensitizing Agents / Q000378:metabolism / Q000633:toxicity*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects
D000890:Anti-Infective Agents; D005456:Fluorescent Dyes; D024841:Fluoroquinolones; D017319:Photosensitizing Agents