scholarly journals Molecular and Biochemical Basis of Minocycline-Induced Hyperpigmentation—The Study on Normal Human Melanocytes Exposed to UVA and UVB Radiation

2021 ◽  
Vol 22 (7) ◽  
pp. 3755
Author(s):  
Jakub Rok ◽  
Zuzanna Rzepka ◽  
Justyna Kowalska ◽  
Klaudia Banach ◽  
Artur Beberok ◽  
...  

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.

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 967
Author(s):  
Micaely Cristina dos Santos Tenório ◽  
Nayara Gomes Graciliano ◽  
Fabiana Andréa Moura ◽  
Alane Cabral Menezes de Oliveira ◽  
Marília Oliveira Fonseca Goulart

N-acetylcysteine (NAC) is a medicine widely used to treat paracetamol overdose and as a mucolytic compound. It has a well-established safety profile, and its toxicity is uncommon and dependent on the route of administration and high dosages. Its remarkable antioxidant and anti-inflammatory capacity is the biochemical basis used to treat several diseases related to oxidative stress and inflammation. The primary role of NAC as an antioxidant stems from its ability to increase the intracellular concentration of glutathione (GSH), which is the most crucial biothiol responsible for cellular redox imbalance. As an anti-inflammatory compound, NAC can reduce levels of tumor necrosis factor-alpha (TNF-α) and interleukins (IL-6 and IL-1β) by suppressing the activity of nuclear factor kappa B (NF-κB). Despite NAC’s relevant therapeutic potential, in several experimental studies, its effectiveness in clinical trials, addressing different pathological conditions, is still limited. Thus, the purpose of this chapter is to provide an overview of the medicinal effects and applications of NAC to human health based on current therapeutic evidence.


2002 ◽  
Vol 15 (5) ◽  
pp. 321-329 ◽  
Author(s):  
Jing Shang ◽  
Jürgen Eberle ◽  
Christoph C. Geilen ◽  
Amir M. Hossini ◽  
Lothar F. Fecker ◽  
...  

2019 ◽  
Vol 28 ◽  
pp. 50-54 ◽  
Author(s):  
Satoshi Yoshimoto ◽  
Yoshiaki Ohagi ◽  
Moemi Yoshida ◽  
Hiroki Yanagi ◽  
Sawako Hibino ◽  
...  

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8583-8583
Author(s):  
F. Meyskens

8583 Our studies of the properties of reactive oxygen species(ROS) in melanomagenesis led us to explore the role of heavy metals in this process. A systematic experimental exploration of the effect of ROS on melanin and melanosomes in melanocytes and melanoma cells using biophysical techniques including electroparamagnetic resonance to measure free radicals and electron microscopy suggests that the conversion of melanin from an anti-oxidant and reducing agent to a pro-oxidant and photoreactive compound is an early pathogenic event that is accompanied by melanosomal disruption that serves as an ongoing organelle source of free radical generation. The involvement of selected heavy metals enhances this process and in conjunction with ultraviolet light can lead to phenotypic changes in normal human melanocytes that resemble dysplatic nevi melanocytes in culture. A re-examination of the non-genetic risk factors for melanoma has identified a large(and neglected) epidemiology that implicates heavy metals and includes markedly increased risks for melanoma in printers/lithographers(4 large studies), electrical industry workers (3 large studies), and hip replacements patients(a large meta-analyses and 2 cohort studies). High levels of cobalt are present in this latter group post-replacement that lasts for years (?indefinitely) Clinical observations (imaging studies) and studies that document the importance of metallothionein expression in primary melanoma and prognosis also offers ancillary support for the involvement of metals in the pathogenesis of melanoma Based on these considerations and the role of copper in the melanin synthesis pathway and the binding characteristics of metals to melanin we propose that the most likely culprits that accounts for a significant contribution to the etiology and pathogenesis of melanoma are Cu+2 and Co+2 and suggests that chelation may be a reasonable strategy for the prevention of melanoma. No significant financial relationships to disclose.


2014 ◽  
Vol 401 (1-2) ◽  
pp. 107-114 ◽  
Author(s):  
Artur Beberok ◽  
Dorota Wrześniok ◽  
Michał Otręba ◽  
Maciej Miliński ◽  
Jakub Rok ◽  
...  

2019 ◽  
Vol 20 (8) ◽  
pp. 1986 ◽  
Author(s):  
Joana R. Lérias ◽  
Georgia Paraschoudi ◽  
Inês Silva ◽  
João Martins ◽  
Eric de Sousa ◽  
...  

Immune responses to human cytomegalovirus (CMV) can be used to assess immune fitness in an individual. Further to its clinical significance in posttransplantation settings, emerging clinical and translational studies provide examples of immune correlates of protection pertaining to anti-CMV immune responses in the context of cancer or infectious diseases, e.g., tuberculosis. In this viewpoint, we provide a brief overview about CMV-directed immune reactivity and immune fitness in a clinical context and incorporate some of our own findings obtained from peripheral blood or tumour-infiltrating lymphocytes (TIL) from patients with advanced cancer. Observations in patients with solid cancers whose lesions contain both CMV and tumour antigen-specific T-cell subsets are highlighted, due to a possible CMV-associated “bystander” effect in amplifying local inflammation and subsequent tumour rejection. The role of tumour-associated antibodies recognising diverse CMV-derived epitopes is also discussed in light of anti-cancer immune responses. We discuss here the use of anti-CMV immune responses as a theranostic tool—combining immunodiagnostics with a personalised therapeutic potential—to improve treatment outcomes in oncological indications.


2004 ◽  
Vol 12 (4) ◽  
pp. 203-205 ◽  
Author(s):  
Milenko Stanojevic ◽  
Zorica Stanojevic ◽  
Dragan Jovanovic ◽  
Milena Stojiljkovic

Light radiation is a part of the electromagnetic radiation, and it consists of the ultraviolet (UV) radiation, visible light, and infrared radiation. UV radiation energy is absorbed in the form of photons in biomolecules (chromophores) and induces various cellular reactions, out of which photochemical and photosensitizing are the most significant. In contact with the skin UV radiation incites protection mechanisms: the most important are stratum corneum thickening and melanin synthesis (melanogenesis). Basic role of melanin is absorption and scattering of UV rays and neutralization of free radicals. In this review physical characteristics of UV radiation, its biological effects, and relation to melanogenesis and carcinogenesis are discussed.


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