Photochemistry of nitric oxide and S-nitrosothiols in human skin

Abstract

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 (NO x). Those are mainly composed of nitrite (NO 2 −), nitrate (NO 3 −), and S-nitrosothiols (RSNOs) which forms a large NO store. These NO x 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 NO 2 − and NO 3 − and mixtures of NO 2 − and glutathione and NO 3 − 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 NO 2 − 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.

What Are Reactive Oxygen Species, Free Radicals, and Oxidative Stress in Skin Diseases?

“…Although the roles of nNOS and eNOS have not yet been elucidated, they have been proposed to function in skin homeostasis, such as epidermal proliferation, keratinization, and the regulation of dermal blood flow. Previous studies demonstrated that iNOS synthesized a large amount of • NO during skin inflammation caused by ultraviolet exposure, psoriasis vulgaris, systemic lupus erythematosus, and wound healing [ 22 , 23 , 24 , 25 ]. iNOS activity was also shown to be significantly elevated in an LPS-induced inflammatory skin disease mouse model ( Figure 4 ) [ 19 ].…”

In focus in HCB

“…Upon stimulation by ultraviolet sunlight, the NO x stores in the skin can be redistributed to the blood stream where they may exert a positive physiological response by lowering vascular blood pressure (Weller 2016). Weller and colleagues have been studying the aspects of this beneficial sunlight-induced process for a number of years (Liu et al 2014;Mowbray et al 2009), and have now investigated the most effective range of ultraviolet wavelengths for generating NO (Pelegrino et al 2020). They used an NO meter with an electrochemical NO sensor to measure the release of free NO x species following irradiation with a range of ultraviolet wavelengths from both a controlled chemical aqueous solution simulacrum and human skin biopsy samples (Fig.…”

Recent progress in the toxicity of nitric oxide-releasing nanomaterials

“…1,2,18 NO interaction with cellular targets can vary based on spatial and temporal distribution of NO influx within tumor cells and tumor microenvironment. 17,19 Thus, key factor linked to modulate the dichotomous effect of NO are the amount of NO released, the time-period and the spatial distribution of this signaling molecule in tumor tissue. 20 In addition, tumor microenvironment and heterogeneity also play an important role in the dichotomous effect of NO.…”

“…3,17 Due to the NO instability, the use of NO donors has been successful used to exogenously delivery NO to a target site, in different biomedical applications. 19,26 The most common classes of NO donors, are sodium nitroprusside, organic nitrite and nitrate, furoxans, benzofuroxans, diazeniumdiolates (NONOates), S-nitrosothiols (RSNOs), Roussin's black salt (RBS) and metal nitrosyl complexes. 3,17,[27][28][29][30][31] The molecular representations of commonly used NO donors are shown in Figure 1.…”

“…26,27 RSNOs is also involved in Stransnitrosation reactions that has been linked to be a relevant step on the downward signaling route created by NO. 19,26,34,35,36 Another commonly used NO donor is the RBS, which is a metal-nitrosyl complex that releases NO after illumination. 31,37 Although NO donors have allowed the use of exogenous NO in biomedical applications, these molecules have limitations regarding the NO concentrations spatially and temporally reach.…”