Beberok Artur, Wrześniok Dorota, Otręba Michał, Miliński Maciej, Rok Jakub, Buszman Ewa
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University of Silesia, Jagiellońska 4, 41-200, Sosnowiec, Poland,
Mol Cell Biochem. 2015 Mar;401(1-2):107-14. doi: 10.1007/s11010-014-2297-7. Epub 2014 Nov 30.
Fluoroquinolone antibiotics provide broad-spectrum coverage for a number of infectious diseases, including respiratory as well as urinary tract infections. One of the important adverse effects of these drugs is phototoxicity which introduces a serious limitation to their use. To gain insight the molecular mechanisms underlying the fluoroquinolones-induced phototoxic side effects, the impact of two fluoroquinolone derivatives with different phototoxic potential, norfloxacin and moxifloxacin, on melanogenesis and antioxidant enzymes activity in normal human melanocytes HEMa-LP was determined. Both drugs induced concentration-dependent loss in melanocytes viability. The value of EC50 for these drugs was found to be 0.5 mM. Norfloxacin and moxifloxacin suppressed melanin biosynthesis; antibiotics were shown to inhibit cellular tyrosinase activity and to reduce melanin content in melanocytes. When comparing the both analyzed fluoroquinolones, it was observed that norfloxacin possesses greater inhibitory effect on tyrosinase activity in melanocytes than moxifloxacin. The extent of oxidative stress in cells was assessed by measuring the activity of antioxidant enzymes: SOD, CAT, and GPx. It was observed that norfloxacin caused higher depletion of antioxidant status in melanocytes when compared with moxifloxacin. The obtained results give a new insight into the mechanisms of fluoroquinolones toxicity directed to pigmented tissues. Moreover, the presented differences in modulation of biochemical processes in melanocytes may be an explanation for various phototoxic activities of the analyzed fluoroquinolone derivatives in vivo.
氟喹诺酮类抗生素对多种传染病具有广谱抗菌作用，包括呼吸道感染和尿路感染。这些药物的重要不良反应之一是光毒性，这严重限制了它们的使用。为深入了解氟喹诺酮类药物引起光毒性副作用的分子机制，测定了两种具有不同光毒性潜力的氟喹诺酮衍生物诺氟沙星和莫西沙星对正常人黑素细胞HEMa-LP黑素生成和抗氧化酶活性的影响。两种药物均诱导黑素细胞活力呈浓度依赖性丧失。发现这些药物的EC50值为0.5 mM。诺氟沙星和莫西沙星抑制黑色素生物合成；抗生素被证明可抑制细胞酪氨酸酶活性并降低黑素细胞中的黑色素含量。比较两种分析的氟喹诺酮类药物时，观察到诺氟沙星对黑素细胞中酪氨酸酶活性的抑制作用比莫西沙星更强。通过测量抗氧化酶SOD、CAT和GPx的活性来评估细胞中的氧化应激程度。观察到与莫西沙星相比，诺氟沙星导致黑素细胞中抗氧化状态的消耗更高。所得结果为氟喹诺酮类药物对色素组织毒性的机制提供了新的见解。此外，黑素细胞中生化过程调节的差异可能解释了所分析的氟喹诺酮衍生物在体内的各种光毒性活性。
