Abstract
Minocycline is a drug which induces skin hyperpigmentation. Its frequency reaches up to 50% of treated patients. The adverse effect diminishes the great therapeutic potential of minocycline, including antibacterial, neuroprotective, anti-inflammatory and anti-cancer actions. It is supposed that an elevated melanin level and drug accumulation in melanin-containing cells are related to skin hyperpigmentation. This study aimed to evaluate molecular and biochemical mechanism of minocycline-induced hyperpigmentation in human normal melanocytes, as well as the contribution of UV radiation to this side effect. The experiments involved the evaluation of cyto- and phototoxic potential of the drug using cell imaging with light and confocal microscopes as well as biochemical and molecular analysis of melanogenesis. We showed that minocycline induced melanin synthesis in epidermal melanocytes. The action was intensified by UV irradiation, especially with the UVB spectrum. Minocycline stimulated the expression of microphthalmia-associated transcription factor (MITF) and tyrosinase (TYR) gene. Higher levels of melanin and increased activity of tyrosinase were also observed in treated cells. Moreover, minocycline triggered the supranuclear accumulation of tyrosinase, similar to UV radiation. The decreased level of premelanosome protein PMEL17 observed in all minocycline-treated cultures suggests disorder of the formation, maturation or distribution of melanosomes. The study revealed that minocycline itself was able to enhance melanin synthesis. The action was intensified by irradiation, especially with the UVB spectrum. Demonstrated results confirmed the potential role of melanin and UV radiation minocycline-induced skin hyperpigmentation.
Highlights
World Health Organization defined an adverse drug reaction (ADR) as “a response to a drug which is noxious and unintended and which occurs at doses normally used in man for the prophylaxis, diagnosis, or therapy of disease, or the modifications of physiological function”
The presented results show that minocycline induces melanogenesis in human normal melanocytes
The effect is related to translational stimulation and the increased level of microphthalmia-associated transcription factor (MITF) and tyrosinase
Summary
World Health Organization defined an adverse drug reaction (ADR) as “a response to a drug which is noxious and unintended and which occurs at doses normally used in man for the prophylaxis, diagnosis, or therapy of disease, or the modifications of physiological function”. The majority of ADRs (about 75–80%) is predictable, non-immunologic, usually dose-dependent and related to the drug pharmacology. The rest of ADRs are idiosyncratic, unpredictable and they may be immune-mediated [1,2]. It was estimated that ADRs are the reason for about 5–6% of hospital admissions and up to 25% of primary care attendances [2,3,4]. Cutaneous adverse drug reactions are thought to be one of the most frequent. Skin-related ADRs require additional treatment, medical management and generate significant costs for the payer as well as for the service provider [5]. In addition to the above, they lead to a decrease in patient comfort and the limitations of drug usage
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