An Immunohistochemical Study on the Role of Oxidative and Nitrosative Stress in Irradiated Skin

Abstract

Background/Aim: The effects of ionizing radiation through the generation of free radicals, reactive aldehydes, and other oxidative and nitrosative by-products account for skin injuries as side effects of radiation therapy (RT). This study aims to identify cellular pathways in oxidative and nitrosative stress in irradiated skin using well-established marker proteins in an immunohistochemical analysis. Materials and Methods: Tissue specimens of 51 patients were obtained during operative access to the neck. Twenty patients (39.2%) received RT prior to the surgical intervention. Immunohistochemical analysis of stable degradation products of reactive oxygen and nitrogen species (RONS), 3-nitrotyrosine, 8-isoprostane, phosphorylated AKT (p-AKT), and phosphorylated extracellular signal-regulated kinase (p-ERK) was performed in specimens which were exposed to RT and those without a history of RT. Results: Immunohistochemical staining showed a significantly increased expression of nitrotyrosine in superficial and basal epidermal regions of interest (ROI), p-AKT in all epidermal ROI, and p-ERK in all the investigated epidermal and dermal ROI, as well as in an overall analysis. No significance could be detected in immunostaining against isoprostane. Discussion: This study summarizes the influence of RONS in RT. Moreover, a detailed histological analysis was able to identify epidermal ROI as a main starting point of RONS in irradiated skin. Even though the role of RONS in high-dose therapeutic radiation remains a subject for further research, these data underlines the crucial role of RONS in high-dose radiation.