Astaxanthin protects against early acute kidney injury in severely burned rats by inactivating the TLR4/MyD88/NF-κB axis and upregulating heme oxygenase-1

Abstract Early acute kidney injury (AKI) contributes to severe morbidity and mortality in critically burned patients. Renal inflammation plays a vital role in the progression of early AKI, acting as a therapeutic target. Astaxanthin (ATX) is a strong antioxidant widely distributed in marine organism...

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Autores principales:	Songxue Guo, Linsen Guo, Quan Fang, Meirong Yu, Liping Zhang, Chuangang You, Xingang Wang, Yong Liu, Chunmao Han
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dee0bf589b3d41e599fea9404c283c05
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spelling	oai:doaj.org-article:dee0bf589b3d41e599fea9404c283c052021-12-02T17:04:07ZAstaxanthin protects against early acute kidney injury in severely burned rats by inactivating the TLR4/MyD88/NF-κB axis and upregulating heme oxygenase-110.1038/s41598-021-86146-w2045-2322https://doaj.org/article/dee0bf589b3d41e599fea9404c283c052021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86146-whttps://doaj.org/toc/2045-2322Abstract Early acute kidney injury (AKI) contributes to severe morbidity and mortality in critically burned patients. Renal inflammation plays a vital role in the progression of early AKI, acting as a therapeutic target. Astaxanthin (ATX) is a strong antioxidant widely distributed in marine organisms that exerts many biological effects in trauma and disease. ATX is also suggested to have anti-inflammatory activity. Hence, we attempted to explore the role of ATX in protecting against early postburn AKI via its anti-inflammatory effects and the related mechanisms. A severely burned model was established for histological and biochemical assessments based on adult male rats. We found that oxidative stress-induced tissue inflammation participated in the development of early AKI after burn injury and that the MyD88-dependent TLR4/NF-κB pathway was activated to regulate renal inflammation. The TLR4 and NF-κB inhibitors TAK242 and PDTC showed similar effects in attenuating burn-induced renal inflammation and early AKI. Upon ATX treatment, the release of inflammatory mediators in the kidneys was downregulated, while the TLR4/MyD88/NF-κB axis was inhibited in a dose-related manner. TAK242 and PDTC could enhance the anti-inflammatory effect of high-dose ATX, whereas lipopolysaccharide (LPS) reversed its action. Furthermore, the expression of heme oxygenase (HO)-1 was upregulated by ATX in a dose-related manner. Collectively, the above data suggest that ATX protects against renal inflammation in a dose-related manner by regulating the TLR4/MyD88/NF-κB axis and HO-1 and ultimately prevents early AKI following severe burns.Songxue GuoLinsen GuoQuan FangMeirong YuLiping ZhangChuangang YouXingang WangYong LiuChunmao HanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Songxue Guo Linsen Guo Quan Fang Meirong Yu Liping Zhang Chuangang You Xingang Wang Yong Liu Chunmao Han Astaxanthin protects against early acute kidney injury in severely burned rats by inactivating the TLR4/MyD88/NF-κB axis and upregulating heme oxygenase-1
description	Abstract Early acute kidney injury (AKI) contributes to severe morbidity and mortality in critically burned patients. Renal inflammation plays a vital role in the progression of early AKI, acting as a therapeutic target. Astaxanthin (ATX) is a strong antioxidant widely distributed in marine organisms that exerts many biological effects in trauma and disease. ATX is also suggested to have anti-inflammatory activity. Hence, we attempted to explore the role of ATX in protecting against early postburn AKI via its anti-inflammatory effects and the related mechanisms. A severely burned model was established for histological and biochemical assessments based on adult male rats. We found that oxidative stress-induced tissue inflammation participated in the development of early AKI after burn injury and that the MyD88-dependent TLR4/NF-κB pathway was activated to regulate renal inflammation. The TLR4 and NF-κB inhibitors TAK242 and PDTC showed similar effects in attenuating burn-induced renal inflammation and early AKI. Upon ATX treatment, the release of inflammatory mediators in the kidneys was downregulated, while the TLR4/MyD88/NF-κB axis was inhibited in a dose-related manner. TAK242 and PDTC could enhance the anti-inflammatory effect of high-dose ATX, whereas lipopolysaccharide (LPS) reversed its action. Furthermore, the expression of heme oxygenase (HO)-1 was upregulated by ATX in a dose-related manner. Collectively, the above data suggest that ATX protects against renal inflammation in a dose-related manner by regulating the TLR4/MyD88/NF-κB axis and HO-1 and ultimately prevents early AKI following severe burns.
format	article
author	Songxue Guo Linsen Guo Quan Fang Meirong Yu Liping Zhang Chuangang You Xingang Wang Yong Liu Chunmao Han
author_facet	Songxue Guo Linsen Guo Quan Fang Meirong Yu Liping Zhang Chuangang You Xingang Wang Yong Liu Chunmao Han
author_sort	Songxue Guo
title	Astaxanthin protects against early acute kidney injury in severely burned rats by inactivating the TLR4/MyD88/NF-κB axis and upregulating heme oxygenase-1
title_short	Astaxanthin protects against early acute kidney injury in severely burned rats by inactivating the TLR4/MyD88/NF-κB axis and upregulating heme oxygenase-1
title_full	Astaxanthin protects against early acute kidney injury in severely burned rats by inactivating the TLR4/MyD88/NF-κB axis and upregulating heme oxygenase-1
title_fullStr	Astaxanthin protects against early acute kidney injury in severely burned rats by inactivating the TLR4/MyD88/NF-κB axis and upregulating heme oxygenase-1
title_full_unstemmed	Astaxanthin protects against early acute kidney injury in severely burned rats by inactivating the TLR4/MyD88/NF-κB axis and upregulating heme oxygenase-1
title_sort	astaxanthin protects against early acute kidney injury in severely burned rats by inactivating the tlr4/myd88/nf-κb axis and upregulating heme oxygenase-1
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/dee0bf589b3d41e599fea9404c283c05
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Astaxanthin protects against early acute kidney injury in severely burned rats by inactivating the TLR4/MyD88/NF-κB axis and upregulating heme oxygenase-1

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