Minocycline Impact on Redox Homeostasis of Normal Human Melanocytes HEMn-LP Exposed to UVA Radiation and Hydrogen Peroxide.

Jakub Rok,Artur Beberok,Dorota Wrześniok,Mateusz Maszczyk,Zuzanna Rzepka

doi:10.3390/ijms22041642

Jakub Rok, Artur Beberok + Show 3 more

Open Access

https://doi.org/10.3390/ijms22041642

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Abstract

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.

Highlights

Oxidative stress is defined as an imbalance between the generation of reactive oxygen species (ROS) and cellular mechanisms of antioxidant defense [1]
The general influence of minocycline on human melanocytes was tested by use of the cell proliferation reagent WST-1 (Figure 1)
It was presented that the tested drug, proportionally to concentration, inhibited cell proliferation, decreased level of reduced thiols, and stimulated the activity of antioxidant enzymes

Summary

Introduction

Oxidative stress is defined as an imbalance between the generation of reactive oxygen species (ROS) and cellular mechanisms of antioxidant defense [1]. ROS play different and important roles in human physiology, pathology, and pharmacology, e.g., in cellular signaling, lipid metabolism, cell proliferation, differentiation, migration, and apoptosis [4,5,6]. Their reactivity may cause the oxidative damage of most biomolecules, including nucleic acids, proteins, lipids, amino acids, or carbohydrates, leading to the cytotoxic effect [7]. Overproduction of ROS is observed in many chronic and acute disorders, including cardiovascular, neurological, and dermatological diseases [8,9,10,11,12,13,14]

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