Cytotoxic effect of lomefloxacin in culture of human epidermal melanocytes

Abstract

Abstract:Backround: 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 ED 50 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. Conclusion: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.

Impact of sparfloxacin on melanogenesis and antioxidant defense system in normal human melanocytes HEMa-LP – An in vitro study

“…Our results indicate that an inhibitory effect of sparfloxacin on melanogenesis is probably due to its direct inhibition of tyrosinase activity. The results of our prior studies [23,24] and those obtained in this study reveal that sparfloxacin demonstrates a greater inhibitory effect on cellular tyrosinase activity than ciprofloxacin or lomefloxacin.…”

“…The value of EC 50 was determined to be $0.25 mM. For the same cell line the value of EC 50 established for ciprofloxacin was 0.5 mM [23] and 0.75 mM for lomefloxacin [24], which indicates that sparfloxacin is significantly more toxic. Melanin is synthesized in the presence of tyrosinase, a coppercontaining metalloglycoprotein which is though to possess multiple catalytic activities utilizing L-tyrosine, dihydroxyphenylalanine (L-DOPA) and 5,6-dihydroxyindole as substrates [33].…”

“…Moreover, we demonstrated that ciprofloxacin [23] and lomefloxacin [24] modulated biochemical processes in normal human melanocytes, suggesting a mechanism for the drug-induced toxicity on pigmented tissues. Whether the same mechanism can be attributed to another fluoroquinolone derivative, i.e., sparfloxacin, with relatively high toxic potential, remains to be determined.…”

“…Previously, we documented that ciprofloxacin [23], lomefloxacin [24], norfloxacin and sparfloxacin [25] formed stable complexes with model synthetic melanin in vitro. Moreover, we demonstrated that ciprofloxacin [23] and lomefloxacin [24] modulated biochemical processes in normal human melanocytes, suggesting a mechanism for the drug-induced toxicity on pigmented tissues.…”

Effect of tetracycline and UV radiation on melanization and antioxidant status of melanocytes

“…Previously, we documented that aminoglycoside antibiotics: amikacin [17], kanamycin [18], netilmicin [19] and streptomycin [20] as well as fluoroquinolones: ciprofloxacin [21] and lomefloxacin [22], suppressed melanin biosynthesis and affected antioxidant enzymes activities in human light pigmented melanocytes. We also documented that nicotine modulated melanin biosynthesis and antioxidant enzymes activities in human dark pigmented melanocytes [23].…”