Wrześniok Dorota, Beberok Artur, Otreba Michał, Buszman Ewa
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University of Silesia, Jagiellońska 4, PL-41-200 Sosnowiec, Poland.
Acta Pol Pharm. 2013 Sep-Oct;70(5):803-8.
It is known that aminoglycoside antibiotics bind well to melanin biopolymer, but the relation between their affinity to melanin and ototoxicity is not well established. The aim of this work was to examine the impact of netilmicin on melanogenesis in cultured normal human melanocytes (HEMa-LP). The WST-1 assay was used to detect netilmicin cytotoxic effect. Netilmicin induced concentration-dependent loss in melanocytes viability. The value of EC50 was found to be - 75.0 mM. The analyzed antibiotic inhibited melanin biosynthesis in a concentration-dependent manner. Increasing the drug concentration resulted also in a decrease of cellular tyrosinase activity. Netilmicin-induced modulation of melanogenesis in melanocytes in vitro may explain a potential role of melanin and melanocytes in the mechanisms of aminoglycosides ototoxic effects in vivo.
已知氨基糖苷类抗生素与黑色素生物聚合物结合良好,但其与黑色素的亲和力和耳毒性之间的关系尚未明确确立。这项工作的目的是研究奈替米星对培养的正常人黑素细胞(HEMa-LP)黑色素生成的影响。采用WST-1法检测奈替米星的细胞毒性作用。奈替米星诱导黑素细胞活力呈浓度依赖性丧失。发现EC50值为-75.0 mM。分析的抗生素以浓度依赖性方式抑制黑色素生物合成。药物浓度增加也导致细胞酪氨酸酶活性降低。奈替米星在体外诱导黑素细胞黑色素生成的调节可能解释了黑色素和黑素细胞在体内氨基糖苷类耳毒性作用机制中的潜在作用。