Sulforaphane-Mediated Nrf2 Activation Prevents Radiation-Induced Skin Injury through Inhibiting the Oxidative-Stress-Activated DNA Damage and NLRP3 Inflammasome.

Jinlong Wei,Yuyu Zhang,Ying Xin,Lingbin Meng,Weiyan Shi,Xin Jiang,Zhuangzhuang Zheng,Qin Zhao,Huanhuan Wang

doi:10.3390/antiox10111850

Abstract

This article mainly observed the protective effect of sulforaphane (SFN) on radiation-induced skin injury (RISI). In addition, we will discuss the mechanism of SFN’s protection on RISI. The RISI model was established by the irradiation of the left thigh under intravenous anesthesia. Thirty-two C57/BL6 mice were randomly divided into control group (CON), SFN group, irradiation (IR) group, and IR plus SFN (IR/SFN) group. At eight weeks after irradiation, the morphological changes of mouse skin tissues were detected by H&E staining. Then, the oxidative stress and inflammatory response indexes in mouse skin tissues, as well as the expression of Nrf2 and its downstream antioxidant genes, were evaluated by ELISA, real-time PCR, and Western blotting. The H&E staining showed the hyperplasia of fibrous tissue in the mouse dermis and hypodermis of the IR group. Western blotting and ELISA results showed that the inflammasome of NLRP3, caspase-1, and IL-1β, as well as oxidative stress damage indicators ROS, 4-HNE, and 3-NT, in the skin tissues of mice in the IR group were significantly higher than those in the control group (p < 0.05). However, the above pathological changes declined sharply after SFN treatment (p < 0.05). In addition, the expressions of Nrf2 and its regulated antioxidant enzymes, including CAT and HO-1, were higher in the skin tissues of SFN and IR/SFN groups, but lower in the control and IR groups (p < 0.05). SFN may be able to suppress the oxidative stress by upregulating the expression and function of Nrf2, and subsequently inhibiting the activation of NLRP3 inflammasome and DNA damage, so as to prevent and alleviate the RISI.

Highlights

In the present study, we investigate whether SFN can prevent Radiation-induced skin injury (RISI) and whether its protection is associated with the inhibition of oxidative-stress-mediated DNA damage and Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation by upregulating Nuclear factor erythroid 2-related factor 2 (Nrf2)
In the IR group, the skin damage was gradually aggravated after initial irradiation
In the IR plus SFN (IR/SFN) group, mice skin only showed a small amount of scattered erythema in 1 w, 4 w, and 8 w (Figure 1A)

Summary

Introduction

Radiotherapy (RT) is currently the main treatment for various cancers. Radiation can bring both short-term and long-term side effects to healthy tissue. Hematological toxicity, skin and mucous membrane damage, and damage to other exposed sites [1]. Radiation-induced skin injury (RISI) is one of the major complications [2]. It has been reported that about 80% of patients with head and neck cancer during RT can present dry or wet dermatitis, mucosal congestion, erosion, ulcers, and other skin mucosal reactions after RT [3]. RISI can affect the dose and Antioxidants 2021, 10, 1850.

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