Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University of Silesia, Sosnowiec, Poland.
Pharmacol Rep. 2013;65(3):689-99. doi: 10.1016/s1734-1140(13)71047-8.
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.
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.
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.
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.
洛美沙星是一种强效杀菌抗生素。该药物在治疗各种感染中的应用伴随着对色素组织的严重不良反应。洛美沙星副作用的确切机制尚未得到很好的确立。本研究旨在描述洛美沙星与黑色素的相互作用，并研究这种相互作用如何影响黑色素细胞中的细胞活力和黑色素形成。
使用正常的人表皮黑色素细胞和 DOPA-黑色素模型。使用分光光度法研究洛美沙星-黑色素复合物的结合参数以及抗生素对色素细胞活力和黑色素形成的影响。
我们的结果表明，洛美沙星与黑色素形成稳定的复合物。对药物与黑色素结合的分析表明，形成这些复合物至少涉及两类独立的结合位点。使用 WST-1 测定法检测抗生素的细胞毒性作用。洛美沙星的 ED50 值约为 0.75mmol/L。已经表明，洛美沙星会抑制酪氨酸酶的活性，并以剂量依赖的方式降低人皮肤黑色素细胞中的黑色素含量。
所分析的氟喹诺酮类药物与黑色素形成复合物的能力，以及在体外黑色素细胞中黑色素形成过程的抑制作用，可能解释了体内由于黑色素组织中积累而导致的洛美沙星不良副作用的机制中黑色素生物聚合物的潜在作用。
