Photochemistry of nitric oxide and S-nitrosothiols in human skin

Milena T Pelegrino,Richard B Weller,Amedea B Seabra,André Paganotti

doi:10.1007/s00418-020-01858-w

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 (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.

Highlights

Nitric oxide (NO) is a small but important molecule in mammalian biology
The generation of free NO from aqueous solutions of NOx species and human skin was measured in real time upon UV irradiation (270–320 nm), using an NO meter with an electrochemical NO sensor
The NO generated from each NOx specie was compared with the levels of NO generated from human skin under the same irradiation condition (Fig. 2)

Summary

Introduction

Nitric oxide (NO) is a small but important molecule in mammalian biology. It is a free radical involved in a wide range of physiological processes, such as the control of blood pressure, neuronal communication, wound healing, and macrophage toxicity against pathogens, among others (Hirai et al 2018; Nagasaka et al 2018). Of its important role in the promotion of vasodilation (Ignarro et al 1987) After this important discovery, NO has been linked with several other physiologic processes with promising implications in the biomedical field. The enzymatic pathways involve the action of nitric oxide synthase enzymes (NOS), which have three isoforms, neuronal (nNOS), endothelial (nNOS) and inducible (iNOS) (Martínez-Ruiz et al 2011; Seabra and Durán 2012; Seabra et al 2015a, b). The nonenzymatic pathway of NO release is important in skin physiology and ultraviolet (UV) light exposure (Martínez-Ruiz et al 2011; Weller 2016; Eilertsen et al 2018)

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