Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 41-200 Sosnowiec, Poland.
Int J Mol Sci. 2021 Feb 6;22(4):1642. doi: 10.3390/ijms22041642.
Minocycline is a semisynthetic tetracycline antibiotic. In addition to its antibacterial activity, minocycline shows many non-antibiotic, beneficial effects, including antioxidative action. The property is responsible, e.g., for anti-inflammatory, neuroprotective, and cardioprotective effects of the drug. However, long-term pharmacotherapy with minocycline may lead to hyperpigmentation of the skin. The reasons for the pigmentation disorders include the deposition of the drug and its metabolites in melanin-containing cells and the stimulation of melanogenesis. The adverse drug reaction raises a question about the influence of the drug on melanocyte homeostasis. The study aimed to assess the effect of minocycline on redox balance in human normal melanocytes HEMn-LP exposed to hydrogen peroxide and UVA radiation. The obtained results indicate that minocycline induced oxidative stress in epidermal human melanocytes. The drug inhibited cell proliferation, decreased the level of reduced thiols, and stimulated the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). The described changes were accompanied by an increase in the intracellular level of ROS. On the other hand, pretreatment with minocycline at the same concentrations increased cell viability and significantly attenuated the oxidative stress in melanocytes exposed to hydrogen peroxide and UVA radiation. Moreover, the molecular docking analysis revealed that the different influence of minocycline and other tetracyclines on CAT activity can be related to the location of the binding site.
米诺环素是一种半合成的四环素类抗生素。除了具有抗菌活性外,米诺环素还具有许多非抗生素的有益作用,包括抗氧化作用。这种特性负责药物的抗炎、神经保护和心脏保护作用。然而,长期使用米诺环素进行药物治疗可能会导致皮肤色素沉着。色素沉着紊乱的原因包括药物及其代谢物在含黑色素细胞中的沉积和黑色素生成的刺激。这种不良反应引起了人们对药物对黑素细胞稳态影响的关注。本研究旨在评估米诺环素对暴露于过氧化氢和 UVA 辐射的人正常黑素细胞 HEMn-LP 中氧化还原平衡的影响。研究结果表明,米诺环素诱导表皮人黑素细胞发生氧化应激。该药物抑制细胞增殖,降低还原型巯基水平,并刺激超氧化物歧化酶 (SOD)、过氧化氢酶 (CAT) 和谷胱甘肽过氧化物酶 (GPx) 的活性。描述的变化伴随着 ROS 细胞内水平的增加。另一方面,用相同浓度的米诺环素预处理可增加细胞活力,并显著减轻暴露于过氧化氢和 UVA 辐射的黑素细胞中的氧化应激。此外,分子对接分析表明,米诺环素和其他四环素类药物对 CAT 活性的不同影响可能与结合位点的位置有关。