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

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/B...

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Autores principales:	Jinlong Wei, Qin Zhao, Yuyu Zhang, Weiyan Shi, Huanhuan Wang, Zhuangzhuang Zheng, Lingbin Meng, Ying Xin, Xin Jiang
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	sulforaphane Nrf2 oxidative stress NLRP3 radiation-induced skin injury Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/a85e56515ffc42a8ad6f9453005d57d3
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spelling	oai:doaj.org-article:a85e56515ffc42a8ad6f9453005d57d32021-11-25T16:29:50ZSulforaphane-Mediated Nrf2 Activation Prevents Radiation-Induced Skin Injury through Inhibiting the Oxidative-Stress-Activated DNA Damage and NLRP3 Inflammasome10.3390/antiox101118502076-3921https://doaj.org/article/a85e56515ffc42a8ad6f9453005d57d32021-11-01T00:00:00Zhttps://www.mdpi.com/2076-3921/10/11/1850https://doaj.org/toc/2076-3921This 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 (<i>p</i> < 0.05). However, the above pathological changes declined sharply after SFN treatment (<i>p</i> < 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 (<i>p</i> < 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.Jinlong WeiQin ZhaoYuyu ZhangWeiyan ShiHuanhuan WangZhuangzhuang ZhengLingbin MengYing XinXin JiangMDPI AGarticlesulforaphaneNrf2oxidative stressNLRP3radiation-induced skin injuryTherapeutics. PharmacologyRM1-950ENAntioxidants, Vol 10, Iss 1850, p 1850 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	sulforaphane Nrf2 oxidative stress NLRP3 radiation-induced skin injury Therapeutics. Pharmacology RM1-950
spellingShingle	sulforaphane Nrf2 oxidative stress NLRP3 radiation-induced skin injury Therapeutics. Pharmacology RM1-950 Jinlong Wei Qin Zhao Yuyu Zhang Weiyan Shi Huanhuan Wang Zhuangzhuang Zheng Lingbin Meng Ying Xin Xin Jiang Sulforaphane-Mediated Nrf2 Activation Prevents Radiation-Induced Skin Injury through Inhibiting the Oxidative-Stress-Activated DNA Damage and NLRP3 Inflammasome
description	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 (<i>p</i> < 0.05). However, the above pathological changes declined sharply after SFN treatment (<i>p</i> < 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 (<i>p</i> < 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.
format	article
author	Jinlong Wei Qin Zhao Yuyu Zhang Weiyan Shi Huanhuan Wang Zhuangzhuang Zheng Lingbin Meng Ying Xin Xin Jiang
author_facet	Jinlong Wei Qin Zhao Yuyu Zhang Weiyan Shi Huanhuan Wang Zhuangzhuang Zheng Lingbin Meng Ying Xin Xin Jiang
author_sort	Jinlong Wei
title	Sulforaphane-Mediated Nrf2 Activation Prevents Radiation-Induced Skin Injury through Inhibiting the Oxidative-Stress-Activated DNA Damage and NLRP3 Inflammasome
title_short	Sulforaphane-Mediated Nrf2 Activation Prevents Radiation-Induced Skin Injury through Inhibiting the Oxidative-Stress-Activated DNA Damage and NLRP3 Inflammasome
title_full	Sulforaphane-Mediated Nrf2 Activation Prevents Radiation-Induced Skin Injury through Inhibiting the Oxidative-Stress-Activated DNA Damage and NLRP3 Inflammasome
title_fullStr	Sulforaphane-Mediated Nrf2 Activation Prevents Radiation-Induced Skin Injury through Inhibiting the Oxidative-Stress-Activated DNA Damage and NLRP3 Inflammasome
title_full_unstemmed	Sulforaphane-Mediated Nrf2 Activation Prevents Radiation-Induced Skin Injury through Inhibiting the Oxidative-Stress-Activated DNA Damage and NLRP3 Inflammasome
title_sort	sulforaphane-mediated nrf2 activation prevents radiation-induced skin injury through inhibiting the oxidative-stress-activated dna damage and nlrp3 inflammasome
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/a85e56515ffc42a8ad6f9453005d57d3
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Sulforaphane-Mediated Nrf2 Activation Prevents Radiation-Induced Skin Injury through Inhibiting the Oxidative-Stress-Activated DNA Damage and NLRP3 Inflammasome

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