RESUMO
The endogenous free radical nitric oxide (NO) plays a pivotal role in the immunological system. NO has already been reported as a potential candidate for use in the treatment of human coronavirus infections, including COVID-19. In fact, inhaled NO has been used in clinical settings for its antiviral respiratory action, and in the regulation of blood pressure to avoid clot formation. In this mini-review, we discuss recent progress concerning the antivirus activity of NO in clinical, pre-clinical and research settings, and its beneficial effects in the treatment of clinical complications in patients infected with coronaviruses and other respiratory viral diseases, including COVID-19. We also highlight promising therapeutic effects of NO donors allied to nanomaterials to combat COVID-19 and other human coronavirus infections. Nanomaterials can be designed to deliver sustained, localized NO release directly at the desired application site, enhancing the beneficial effects of NO and minimizing the side effects. Challenges and perspectives are presented to open new fields of research.
Assuntos
Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Nanopartículas/uso terapêutico , Óxido Nítrico/uso terapêutico , Administração por Inalação , Antivirais/administração & dosagem , Infecções por Coronavirus/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Humanos , Nanopartículas/administração & dosagem , Óxido Nítrico/administração & dosagemRESUMO
Nitric oxide (NO) is related to a wide range of physiological processes such as vasodilation, macrophages cytotoxicity and wound healing. The human skin contains NO precursors (NOx). Those are mainly composed of nitrite (NO2-), nitrate (NO3-), and S-nitrosothiols (RSNOs) which forms a large NO store. These NOx stores in human skin can mobilize NO to blood stream upon ultraviolet (UV) light exposure. The main purpose of this study was to evaluate the most effective UV light wavelength to generate NO and compare it to each NO precursor in aqueous solution. In addition, the UV light might change the RSNO content on human skin. First, we irradiated pure aqueous solutions of NO2- and NO3- and mixtures of NO2- and glutathione and NO3- and S-nitrosoglutathione (GSNO) to identify the NO release profile from those species alone. In sequence, we evaluated the NO generation profile on human skin slices. Human skin was acquired from redundant plastic surgical samples and the NO and RSNO measurements were performed using a selective NO electrochemical sensor. The data showed that UV light could trigger the NO generation in skin with a peak at 280-285 nm (UVB range). We also observed a significant RSNO formation in irradiated human skin, with a peak at 320 nm (UV region) and at 700 nm (visible region). Pre-treatment of the human skin slice using NO2- and thiol (RSHs) scavengers confirmed the important role of these molecules in RSNO formation. These findings have important implications for clinical trials with potential for new therapies.
Assuntos
Óxido Nítrico/biossíntese , S-Nitrosotióis/metabolismo , Pele/metabolismo , Pele/efeitos da radiação , Raios Ultravioleta , Humanos , Processos FotoquímicosRESUMO
Nitric oxide (NO) is a crucial molecule in the human body. The encapsulation of exogenous NO donors into chitosan nanoparticles (CS NPs) has been widely used to overcome NO drawbacks in pharmacological applications, such as, its short half-life. The NO donor, S-nitrosoglutathione (GSNO), was encapsulated into CS NPs (GSNO-CS NPs) and characterized by AFM and DLS measurements. The nanoparticles presented a hydrodynamic size of 123.3 ± 1.5 nm and a polydispersity of 0.25 ± 0.01. The ability of GSNO-CS NPs, combined with UV irradiation, to deliver NO was evaluated using ex vivo human skin. The human skin was pre-treated with GSNO-CS NPs, in the presence and absence of UV irradiation. The results showed that the combined treatment significantly increased the NO and S-nitrosothiol levels in human skin. This effect can emulate the cardiovascular benefits related to NO without negative side effects of skin exposure to UV light.
Assuntos
Quitosana/química , Nanopartículas/química , Doadores de Óxido Nítrico/química , Óxido Nítrico/farmacologia , S-Nitrosoglutationa/química , Pele/efeitos dos fármacos , Humanos , Hidrodinâmica , Óxido Nítrico/química , Tamanho da Partícula , Propriedades de Superfície , Raios UltravioletaRESUMO
Melanoma is a malignant proliferative disease originated from melanocyte transformations, which are characterized by a high metastatic rate and mortality. Advances in Nanotechnology have provided useful new approaches and tools for antitumor chemotherapy. The aim of this study was to investigate the molecular mechanisms underlying chitosan nanoparticles containing S-nitrosomercaptosuccinic acid ( S-nitroso-MSA-CS) induced cytotoxicity in melanoma cells. S-Nitroso-MSA-CS induced concentration-dependent cell death against B16-F10 tumor cells, whereas non-nitroso nanoparticles (CS or MSA-CS) did not induce significant cytotoxicity. Additionally, melanoma cells were more sensitive to cell death than normal melanocytes. S-Nitroso-MSA-CS-induced cytotoxicity exhibited features of caspase-dependent apoptosis, and it was associated with oxidative stress, characterized by increased mitochondrial superoxide production and oxidation of protein thiol groups. In addition, tyrosine nitration and cysteine S-nitrosylation of amino acid residues in cellular proteins were observed. The potential use of these nanoparticles in antitumor chemotherapy of melanoma is discussed.