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Histochem Cell Biol
2020 Jun 01;1536:431-441. doi: 10.1007/s00418-020-01858-w.
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Photochemistry of nitric oxide and S-nitrosothiols in human skin.
Pelegrino MT
,
Paganotti A
,
Seabra AB
,
Weller RB
.
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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.
Fig. 1. Contour maps of NO generated from irradiated aqueous solutions of (i) NO2− (0.05 mmol L−1, pH 4.5), (ii) NO3− (2.0 mmol L−1, pH 4.5), (iii) a mixture of NO2− (0.05 mmol L−1, pH 4.5) + GSNO (1.0 mmol L−1, pH 4.5), and (iv) a mixture of NO3− (2.0 mmol L−1, pH 4.5) + GSH (1.0 mmol L−1, pH 4.5). The measurement of NO generated was performed using the NO meter with an electrochemical sensor. SN is the normalized signal of free NO generated. The colors red, orange and yellow indicate high levels of NO, the green color indicates an intermediary level of NO, and the colors dark blue, light blue and purple indicate a low level of NO in each tested wavelength (250–330 nm) in function of the applied energy (0 to 10 J cm−2)
Fig. 2. Contour maps of free NO generated from human skin irradiated at 250–320 nm. The measurement of NO was performed using the NO meter with an electrochemical sensor. SN is the normalized signal of free NO generated. The colors red, orange and yellow indicate a high level of NO, the green indicates an intermediary level of NO, and the colors dark blue, light blue and purple indicate a low level of NO in function of the applied energy (0 to 10 J cm−2)
Fig. 3. Free NO release response to dose of energy (NODR) from aqueous solutions of (i) NO2− (0.05 mmol L−1, pH 4.5), (ii) NO3− (2.0 mmol L−1, pH 4.5), (iii) a mixture of NO2− (0.05 mmol L−1, pH 4.5) + GSNO (1.0 mmol L−1, pH 4.5), (iv) a mixture of NO3− (2.0 mmol L−1, pH 4.5) + GSH (1.0 mmol L−1, pH 4.5), and (v) human skin slice (4 mm). The NODR was calculated through the curve slope of NO signal (SNO) versus energy dose (ED)
Fig. 4. Presence of RSNOs on human skin upon light irradiation divided in a ultraviolet irradiation (290–400 nm) and b visible (401–700 nm) and infrared (701–800 nm) irradiation. The grey dotted line represents the S-nitrosothiols basal level in the healthy human skin at 35.14 μmol L−1
Fig. 5. S-nitrosothiols concentrations in human skin after irradiation at 320 nm (UVA) and at 700 nm (Visible) in comparison with the control group (skin in the dark). The skin samples were preincubated with sulfanilamide (SNM) or N-ethylmaleimide (NEM) both at 0.5 mmol L−1 for 1 h at 25 °C in the dark before the irradiation. SNM is a NO2− scavenger and NEM is thiol scavenger
Fig. 6. S-nitrosothiols concentration in human skin after irradiation at 320 nm (UVA) in comparison with the control (dark). The skin samples were pre-incubated with a solution of NaNO3 at different concentrations (50, 500, 1000 and 5000 μmol L−1) for 1 h at 25 °C in the dark
Scheme 1. Main pathways of S-nitrosothiols (RSNO) formation in a biological environment
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