Photophysical and phototoxic properties of the antibacterial fluoroquinolones levofloxacin and moxifloxacin.
Two antibacterial fluoroquinolones, levofloxacin and moxifloxacin, were investigated to evaluate their photophysical properties and to explore the mechanism of their phototoxicity. Photophysical experiments were carried out in aqueous solution by stationary and time-resolved fluorimetry, and by laser flash photolysis, to obtain information on the various decay pathways of the excited states of the drugs and on transient species formed upon irradiation. The results obtained show that levofloxacin is able to photosensitize red blood cell lysis in an oxygen-independent way and induce a high decrease in cell viability after UVA irradiation, although to a lesser degree than the racemic mixture ofloxacin. Moxifloxacin, which is an 8-MeO-substituted fluoroquinolone, is less phototoxic than the other compounds. Cellular phototoxicity was inhibited by the addition of superoxide dismutase, catalase, and free radical and hydroxyl radical scavengers (BHA, GSH, mannitol, and DMTU), indicating the involvement of superoxide anion and/or a radical mechanism in their cytotoxicity. A good correlation was observed between lipid peroxidation, protein photodamage, and cellular phototoxicity, indicating that test compounds exert their toxic effects mainly in the cellular membrane. Experiments carried out on pBR322 DNA show that these derivatives do not significantly photocleave DNA directly, but single-strand breaks were evidenced after treatment of photosensitized DNA by two base-excision-repair enzymes, and Endo III.
Viola
Giampietro
G
Department of Pharmaceutical Sciences, University of Padova, via Marzolo 5, I-35131 Padova. giampietro.viola.1@unipd.it
Facciolo
Laura
L
Canton
Marcella
M
Vedaldi
Daniela
D
Dall'Acqua
Francesco
F
Aloisi
Gian Gaetano
GG
Amelia
Matteo
M
Barbafina
Arianna
A
Elisei
Fausto
F
Latterini
Loredana
L
D016475:3T3 Cells; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*; D001372:Aza Compounds / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*; D004307:Dose-Response Relationship, Radiation; D004912:Erythrocytes / Q000187:drug effects / Q000528:radiation effects; D024841:Fluoroquinolones / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*; D006801:Humans; D064704:Levofloxacin; D015227:Lipid Peroxidation / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D008807:Mice, Inbred BALB C; D000077266:Moxifloxacin; D015242:Ofloxacin / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*; D010782:Photolysis / Q000187:drug effects; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*; D014466:Ultraviolet Rays
D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D017319:Photosensitizing Agents; D011804:Quinolines; D064704:Levofloxacin; D015242:Ofloxacin; D000077266:Moxifloxacin