Rzepka Zuzanna, Karkoszka-Stanowska Marta, Marciniec Krzysztof, Zdybel Magdalena, Pilawa Barbara, Wrześniok Dorota
Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, Jagiellońska 4, 41-200 Sosnowiec, Poland.
Department of Organic Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, Jagiellońska 4, 41-200 Sosnowiec, Poland.
Int J Mol Sci. 2025 Sep 13;26(18):8939. doi: 10.3390/ijms26188939.
Tigecycline is an antibiotic belonging to the glycylcycline group of tetracyclines. Similar to other tetracycline derivatives, tigecycline is used in dermatology because of its bacteriostatic effect. Despite an overall favorable safety profile, tetracyclines are associated with a spectrum of cutaneous adverse effects, notably pigmentary disorders and phototoxic reactions. These dermatologic manifestations are presumed to result from tigecycline's affinity for melanin biopolymer and its subsequent accumulation within the pigment-containing tissues. This study aimed to assess the impact of tigecycline on human normal skin cell homeostasis varied by melanin content. The study was conducted on HEMn-LP melanocytes and human dermal fibroblasts. The aim was achieved by determining the cell number, cell cycle, mitochondrial potential, and redox homeostasis and determining in silico the possibility of binding tigecycline to melanin biopolymers. In this study, it was shown that the cells more sensitive to tigecycline were HEMn-LP melanocytes. The obtained results showed that tigecycline decreased cell number in a dose-dependent manner. In addition, tigecycline was shown to reduce mitochondrial potential, increase the level of oxidized thiols, and increase ROS content in melanocytes, contributing to oxidative stress. In silico studies have shown that the binding of tigecycline to melanin may play a role in the induction of the toxic effects of tigecycline on the skin.
替加环素是一种属于四环素类甘氨酰环素组的抗生素。与其他四环素衍生物类似,替加环素因其抑菌作用而用于皮肤科。尽管总体安全性良好,但四环素类药物会引发一系列皮肤不良反应,尤其是色素紊乱和光毒性反应。这些皮肤表现被认为是由于替加环素对黑色素生物聚合物的亲和力及其随后在含色素组织中的蓄积所致。本研究旨在评估替加环素对因黑色素含量不同而变化的人正常皮肤细胞稳态的影响。该研究在HEMn-LP黑色素细胞和人真皮成纤维细胞上进行。通过测定细胞数量、细胞周期、线粒体电位和氧化还原稳态,并通过计算机模拟确定替加环素与黑色素生物聚合物结合的可能性来实现这一目标。在本研究中,结果表明对替加环素更敏感的细胞是HEMn-LP黑色素细胞。所得结果表明,替加环素以剂量依赖性方式减少细胞数量。此外,替加环素被证明会降低线粒体电位,增加氧化型硫醇水平,并增加黑色素细胞中的活性氧含量,从而导致氧化应激。计算机模拟研究表明,替加环素与黑色素的结合可能在替加环素对皮肤毒性作用的诱导中起作用。