title: Interaction between ciprofloxacin and melanin: the effect on proliferation and melanization in melanocytes.
abstract: There have been described serious adverse events caused by ciprofloxacin in pigmented tissues. It is known that some fluoroquinolones bind well to melanin rich tissues, but the relation between their affinity to melanin and the skin or eye toxicity is not well documented. The aim of this study was to examine whether ciprofloxacin binds to melanin, and how this interaction affects the proliferation and melanization in melanocytes. We have demonstrated that complexes which ciprofloxacin forms with melanin possess at least two classes of independent binding sites. Their association constants are K(1)~10(5) M(-1) and K(2)~10(2) M(-1), respectively. Ciprofloxacin has induced evident concentration-dependent loss in melanocytes viability. The value of ED(50) was found to be ~0.5 mM. It has also been shown that ciprofloxacin reduces melanin content, and decreases tyrosinase activity in human skin melanocytes. The ability of ciprofloxacin to interact with melanin and its inhibitory effect on melanization in melanocytes in vitro may explain a potential role of melanin in the mechanisms of ciprofloxacin toxic effects in vivo.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University of Silesia, Jagiellońska 4, PL 41–200 Sosnowiec, Poland.
authors.forename: Artur
authors.initials: A
authors.lastname: Beberok
authors.forename: Ewa
authors.initials: E
authors.lastname: Buszman
authors.forename: Dorota
authors.initials: D
authors.lastname: Wrześniok
authors.forename: Michał
authors.initials: M
authors.lastname: Otręba
authors.forename: Janina
authors.initials: J
authors.lastname: Trzcionka
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D001665:Binding Sites; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002939:Ciprofloxacin / Q000494:pharmacology*; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008543:Melanins / Q000378:metabolism*; D008544:Melanocytes / Q000187:drug effects* / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000378:metabolism
chemical_list: D000890:Anti-Infective Agents; D008543:Melanins; D002939:Ciprofloxacin; D004295:Dihydroxyphenylalanine; C040616:DOPA melanin; D014442:Monophenol Monooxygenase