Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University of Silesia, Jagiellońska 4, PL 41–200 Sosnowiec, Poland.
Eur J Pharmacol. 2011 Nov 1;669(1-3):32-7. doi: 10.1016/j.ejphar.2011.08.003. Epub 2011 Aug 19.
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.
已有报道称，环丙沙星在色素组织中会引起严重的不良反应。已知一些氟喹诺酮类药物与富含黑色素的组织结合良好，但它们与黑色素的亲和力与皮肤或眼睛毒性之间的关系尚未得到很好的证实。本研究旨在探讨环丙沙星是否与黑色素结合，以及这种相互作用如何影响黑色素细胞的增殖和黑色素化。我们已经证明，环丙沙星与黑色素形成的复合物至少具有两类独立的结合位点。它们的结合常数分别为 K(1)10(5) M(-1)和 K(2)10(2) M(-1)。环丙沙星诱导了黑色素细胞活力的明显浓度依赖性丧失。ED(50)值约为 0.5 mM。还表明，环丙沙星降低了人皮肤黑色素细胞中的黑色素含量和酪氨酸酶活性。环丙沙星与黑色素相互作用的能力及其对黑色素细胞中黑色素化的抑制作用，可能解释了黑色素在环丙沙星体内毒性作用机制中的潜在作用。
