Gold-quercetin nanoparticles prevent metabolic endotoxemia-induced kidney injury by regulating TLR4/NF-kB signaling and Nrf2 pathway in high fat diet fed mice

Min-Xuan Xu,1,2,* Ming Wang,3,* Wei-Wei Yang4 1Chongqing Key Laboratory of Medicinal Resources in the Three Gorges Reservoir Region, School of Biological and Chemical Engineering, Chongqing University of Education, Chongqing, 2College of Engineering and Applied Sciences, Nanjing University, Nanjing...

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Autores principales:	Xu MX, Wang M, Yang WW
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	Gold-quercetin nanoparticles kidney injury podocytes TLR4/NF-κB Nrf2 Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/c397a819775a41aca0464768f934c269
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spelling	oai:doaj.org-article:c397a819775a41aca0464768f934c2692021-12-02T01:32:49ZGold-quercetin nanoparticles prevent metabolic endotoxemia-induced kidney injury by regulating TLR4/NF-kB signaling and Nrf2 pathway in high fat diet fed mice1178-2013https://doaj.org/article/c397a819775a41aca0464768f934c2692017-01-01T00:00:00Zhttps://www.dovepress.com/gold-quercetin-nanoparticles-prevent-metabolic-endotoxemia-induced-kid-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Min-Xuan Xu,1,2,* Ming Wang,3,* Wei-Wei Yang4 1Chongqing Key Laboratory of Medicinal Resources in the Three Gorges Reservoir Region, School of Biological and Chemical Engineering, Chongqing University of Education, Chongqing, 2College of Engineering and Applied Sciences, Nanjing University, Nanjing, 3Department of Urology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 4Department of Nephrology, Huai’an First People’s Hospital, Nanjing Medical University, Jiangsu, People’s Republic of China *These authors contributed equally to this work Abstract: High-fat diet-induced metabolic syndrome followed by chronic kidney disease caused by intestinal endotoxemia have received extensive attention. Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) and oxidative stress-related Nrf2/Keap1 were regarded as the key target points involved in metabolic inflammation and kidney injury. However, the molecular mechanism of interaction between TLR4/NF-κB and Nrf2 activation in high-fat diet-induced renal injury is not absolutely understood. Quercetin, a natural product, has been reported to possess antitumor and anti-inflammatory effects. In this regard, this study attempted to prepare poly(d,l-lactide-co-glycolide)-loaded gold nanoparticles precipitated with quercetin (GQ) to investigate the anti-inflammatory and anti-oxidative stress effects in high-fat diet-induced kidney failure. For this study, C57BL/6 mice fed fat-rich fodder were used as the metabolic syndrome model to evaluate the protective effects of GQ on kidney injury and to determine whether TLR4/NF-κB and Nrf2 pathways were associated with the process. Moreover, histological examinations, enzyme-linked immunosorbent assay, Western blot, and basic blood tests and systemic inflammation-related indicators were used to investigate the inhibitory effects of GQ and underlying molecular mechanism by which it may reduce renal injury. Of note, podocyte injury was found to participate in endotoxin-stimulated inflammatory response. TLR4/NF-κB and Nrf2 pathways were upregulated with high-fat diet intake in mice, resulting in reduction of superoxide dismutase activity and increase in superoxide radical, H2O2, malondialdehyde, XO, XDH, and XO/XDH ratio. In addition, upregulation of TLR4/NF-κB and oxidative stress by endotoxin were observed in vitro, which were suppressed by GQ administration, ultimately alleviating podocyte injury. These findings indicated that GQ could restore the metabolic disorders caused by high-fat diet, which suppresses insulin resistance, lipid metabolic imbalance, and proinflammatory cytokine production. Also, it may prevent kidney injury by inhibition of TLR4/NF-κB and oxidative stress, further increasing superoxide dismutase activity. Keywords: gold-quercetin nanoparticles, kidney injury, podocytes, TLR4/NF-κB, Nrf2Xu MXWang MYang WWDove Medical PressarticleGold-quercetin nanoparticleskidney injurypodocytesTLR4/NF-κBNrf2Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 327-345 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Gold-quercetin nanoparticles kidney injury podocytes TLR4/NF-κB Nrf2 Medicine (General) R5-920
spellingShingle	Gold-quercetin nanoparticles kidney injury podocytes TLR4/NF-κB Nrf2 Medicine (General) R5-920 Xu MX Wang M Yang WW Gold-quercetin nanoparticles prevent metabolic endotoxemia-induced kidney injury by regulating TLR4/NF-kB signaling and Nrf2 pathway in high fat diet fed mice
description	Min-Xuan Xu,1,2,* Ming Wang,3,* Wei-Wei Yang4 1Chongqing Key Laboratory of Medicinal Resources in the Three Gorges Reservoir Region, School of Biological and Chemical Engineering, Chongqing University of Education, Chongqing, 2College of Engineering and Applied Sciences, Nanjing University, Nanjing, 3Department of Urology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 4Department of Nephrology, Huai’an First People’s Hospital, Nanjing Medical University, Jiangsu, People’s Republic of China *These authors contributed equally to this work Abstract: High-fat diet-induced metabolic syndrome followed by chronic kidney disease caused by intestinal endotoxemia have received extensive attention. Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) and oxidative stress-related Nrf2/Keap1 were regarded as the key target points involved in metabolic inflammation and kidney injury. However, the molecular mechanism of interaction between TLR4/NF-κB and Nrf2 activation in high-fat diet-induced renal injury is not absolutely understood. Quercetin, a natural product, has been reported to possess antitumor and anti-inflammatory effects. In this regard, this study attempted to prepare poly(d,l-lactide-co-glycolide)-loaded gold nanoparticles precipitated with quercetin (GQ) to investigate the anti-inflammatory and anti-oxidative stress effects in high-fat diet-induced kidney failure. For this study, C57BL/6 mice fed fat-rich fodder were used as the metabolic syndrome model to evaluate the protective effects of GQ on kidney injury and to determine whether TLR4/NF-κB and Nrf2 pathways were associated with the process. Moreover, histological examinations, enzyme-linked immunosorbent assay, Western blot, and basic blood tests and systemic inflammation-related indicators were used to investigate the inhibitory effects of GQ and underlying molecular mechanism by which it may reduce renal injury. Of note, podocyte injury was found to participate in endotoxin-stimulated inflammatory response. TLR4/NF-κB and Nrf2 pathways were upregulated with high-fat diet intake in mice, resulting in reduction of superoxide dismutase activity and increase in superoxide radical, H2O2, malondialdehyde, XO, XDH, and XO/XDH ratio. In addition, upregulation of TLR4/NF-κB and oxidative stress by endotoxin were observed in vitro, which were suppressed by GQ administration, ultimately alleviating podocyte injury. These findings indicated that GQ could restore the metabolic disorders caused by high-fat diet, which suppresses insulin resistance, lipid metabolic imbalance, and proinflammatory cytokine production. Also, it may prevent kidney injury by inhibition of TLR4/NF-κB and oxidative stress, further increasing superoxide dismutase activity. Keywords: gold-quercetin nanoparticles, kidney injury, podocytes, TLR4/NF-κB, Nrf2
format	article
author	Xu MX Wang M Yang WW
author_facet	Xu MX Wang M Yang WW
author_sort	Xu MX
title	Gold-quercetin nanoparticles prevent metabolic endotoxemia-induced kidney injury by regulating TLR4/NF-kB signaling and Nrf2 pathway in high fat diet fed mice
title_short	Gold-quercetin nanoparticles prevent metabolic endotoxemia-induced kidney injury by regulating TLR4/NF-kB signaling and Nrf2 pathway in high fat diet fed mice
title_full	Gold-quercetin nanoparticles prevent metabolic endotoxemia-induced kidney injury by regulating TLR4/NF-kB signaling and Nrf2 pathway in high fat diet fed mice
title_fullStr	Gold-quercetin nanoparticles prevent metabolic endotoxemia-induced kidney injury by regulating TLR4/NF-kB signaling and Nrf2 pathway in high fat diet fed mice
title_full_unstemmed	Gold-quercetin nanoparticles prevent metabolic endotoxemia-induced kidney injury by regulating TLR4/NF-kB signaling and Nrf2 pathway in high fat diet fed mice
title_sort	gold-quercetin nanoparticles prevent metabolic endotoxemia-induced kidney injury by regulating tlr4/nf-kb signaling and nrf2 pathway in high fat diet fed mice
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/c397a819775a41aca0464768f934c269
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Gold-quercetin nanoparticles prevent metabolic endotoxemia-induced kidney injury by regulating TLR4/NF-kB signaling and Nrf2 pathway in high fat diet fed mice

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