Cytotoxic effect of lomefloxacin in culture of human epidermal melanocytes.
BACKGROUND
Lomefloxacin is a potent bactericidal antibiotic. The use of this drug in treatment of various infections is accompanied by serious adverse effects on pigmented tissues. The exact mechanisms of lomefloxacin side effects have not been well established yet. The aim of this study was to characterize the interaction between lomefloxacin and melanin, and to examine how this interaction affects the cell viability and melanization in melanocytes.


METHODS
Normal human epidermal melanocytes and the model DOPA-melanin were used. The binding parameters of lomefloxacin-melanin complexes as well as the antibiotic effect on cell viability and melanization in pigmented cells were investigated using a spectrophotometric method.


RESULTS
Our results indicate that lomefloxacin forms stable complexes with melanin. The analysis of drug binding to melanin has shown that at least two classes of independent binding sites are involved in formation of these complexes. The WST-1 assay was used to detect the antibiotic cytotoxic effect. The value of ED50 for lomefloxacin was about 0.75 mmol/l. It has been shown that lomefloxacin causes inhibition of tyrosinase activity, and reduces melanin content in human skin melanocytes in a dose-dependent manner.


CONCLUSIONS
The ability of the analyzed fluoroquinolone to form complexes with melanin, and the demonstrated inhibitory effect on a melanization process in melanocytes in vitro may explain a potential role of melanin biopolymer in the mechanisms of undesirable side effects of lomefloxacin in vivo resulting from its accumulation in pigmented tissues.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University of Silesia, Sosnowiec, Poland.
Artur
A
Beberok
Michał
M
Otręba
Dorota
D
Wrześniok
Ewa
E
Buszman
D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000378:metabolism; D001665:Binding Sites; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D024841:Fluoroquinolones / Q000009:adverse effects* / Q000378:metabolism*; D006801:Humans; D008543:Melanins / Q000378:metabolism; D008544:Melanocytes / Q000187:drug effects* / Q000378:metabolism; D012867:Skin / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D008543:Melanins; C053091:lomefloxacin