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卡那霉素对黑素细胞中黑色素生成和抗氧化酶活性的影响——一项体外研究。

Impact of kanamycin on melanogenesis and antioxidant enzymes activity in melanocytes--an in vitro study.

机构信息

Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Medical University of Silesia, Jagiellońska 4, PL 41-200, Sosnowiec, Poland.

出版信息

J Cell Biochem. 2013 Dec;114(12):2746-52. doi: 10.1002/jcb.24623.

Abstract

Aminoglycosides, broad spectrum aminoglycoside antibiotics, are used in various infections therapy due to their good antimicrobial characteristics. However, their adverse effects such as nephrotoxicity and auditory ototoxicity, as well as some toxic effects directed to pigmented tissues, complicate the use of these agents. This study was undertaken to investigate the effect of aminoglycoside antibiotic-kanamycin on viability, melanogenesis and antioxidant enzymes activity in cultured human normal melanocytes (HEMa-LP). It has been demonstrated that kanamycin induces concentration-dependent loss in melanocytes viability. The value of EC50 was found to be ~6.0 mM. Kanamycin suppressed melanin biosynthesis: antibiotic was shown to inhibit cellular tyrosinase activity and to reduce melanin content in normal human melanocytes. Significant changes in the cellular antioxidant enzymes: SOD, CAT and GPx were stated in melanocytes exposed to kanamycin. Moreover, it was observed that kanamycin caused depletion of antioxidant defense sytem. It is concluded that the inhibitory effect of kanamycin on melanogenesis and not sufficient antioxidant defense mechanism in melanocytes in vitro may explain the potential mechanisms of undesirable side effects of this drug directed to pigmented tissues in vivo.

摘要

氨基糖苷类抗生素,广谱氨基糖苷类抗生素,由于其良好的抗菌特性,被用于各种感染的治疗。然而,它们的不良反应,如肾毒性和耳毒性,以及一些针对色素组织的毒性作用,使这些药物的使用变得复杂。本研究旨在探讨氨基糖苷类抗生素-卡那霉素对体外培养的正常人黑素细胞(HEMa-LP)活力、黑素生成和抗氧化酶活性的影响。结果表明,卡那霉素诱导黑素细胞活力呈浓度依赖性丧失。EC50 值约为 6.0mM。卡那霉素抑制黑色素生物合成:该抗生素显示出抑制细胞酪氨酸酶活性,并减少正常人黑素细胞中的黑色素含量。暴露于卡那霉素的黑素细胞中细胞抗氧化酶:SOD、CAT 和 GPx 发生了显著变化。此外,还观察到卡那霉素导致抗氧化防御系统耗竭。结论是,卡那霉素对黑素生成的抑制作用和体外黑素细胞中不足的抗氧化防御机制可能解释了该药物在体内对色素组织产生不良副作用的潜在机制。

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