Wrześniok Dorota, Beberok Artur, Otręba Michał, Buszman Ewa
Department of Pharmaceutical Chemistry, Medical University of Silesia in Katowice , Sosnowiec , Poland.
Cutan Ocul Toxicol. 2015;34(2):107-11. doi: 10.3109/15569527.2014.910803. Epub 2014 Jun 18.
Aminoglycoside antibiotics, including gentamicin, despite their ability to induce adverse effects on pigmented tissues, remain valuable and sometimes indispensable for the treatment of various infections. It is known that gentamicin binds to melanin biopolymers, but the relation between this drug affinity to melanin and its toxicity is not well documented. The aim of this work was to examine the impact of gentamicin on viability and melanogenesis in HEMa-LP (light pigmented) and HEMn-DP (dark pigmented) normal human melanocytes.
METHODOLOGY/PRINCIPAL FINDINGS: The effect of gentamicin on cell viability was determined by 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1) assay; melanin content and tyrosinase activity were measured spectrophotometrically. It has been demonstrated that gentamicin induces concentration-dependent loss in melanocytes viability. The application of antibiotic in concentration of 10 mM causes higher reduction in viability of the light pigmented melanocytes (by about 74%) when compared with the dark pigmented ones (by about 62%). The value of the concentration of a drug that produces loss in cell viability by 50% (EC50) for both cell lines was found to be ∼7.5 mM. It has been shown that gentamicin causes inhibition of tyrosinase activity and reduces melanin content in light pigmented melanocytes significantly more than in the dark pigmented cells.
CONCLUSION/SIGNIFICANCE: We have found that gentamicin modulates melanization process in melanocytes in vitro, what may explain the potential role of melanin biopolymer in the mechanisms of undesirable toxic effects of this drug in vivo, as a result of its accumulation in pigmented tissues. We have also stated that the melanogenesis process in light pigmented melanocytes is more sensitive to the inhibitory effect of gentamicin than in the dark pigmented cells.
氨基糖苷类抗生素，包括庆大霉素，尽管它们会对色素组织产生不良影响，但对于各种感染的治疗仍然很有价值，有时甚至不可或缺。已知庆大霉素会与黑色素生物聚合物结合，但这种药物对黑色素的亲和力与其毒性之间的关系尚无充分记录。这项工作的目的是研究庆大霉素对HEMa-LP（浅色色素）和HEMn-DP（深色色素）正常人黑素细胞活力和黑色素生成的影响。
方法/主要发现：通过4-[3-(4-碘苯基)-2-(4-硝基苯基)-2H-5-四氮唑]-1,3-苯二磺酸盐（WST-1）测定法确定庆大霉素对细胞活力的影响；用分光光度法测量黑色素含量和酪氨酸酶活性。已证明庆大霉素会导致黑素细胞活力呈浓度依赖性丧失。与深色色素黑素细胞（约62%）相比，10 mM浓度的抗生素应用导致浅色色素黑素细胞活力降低更高（约74%）。发现两种细胞系导致细胞活力丧失50%（EC50）的药物浓度值约为7.5 mM。已表明庆大霉素对酪氨酸酶活性的抑制作用以及对浅色色素黑素细胞中黑色素含量的降低作用明显大于深色色素细胞。
结论/意义：我们发现庆大霉素在体外调节黑素细胞中的黑色素化过程，这可能解释了黑色素生物聚合物在该药物在体内产生不良毒性作用机制中的潜在作用，这是由于其在色素组织中的积累。我们还指出，浅色色素黑素细胞中的黑色素生成过程比深色色素细胞对庆大霉素的抑制作用更敏感。
