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Dimethyl fumarate ameliorates endotoxin-induced acute kidney injury against macrophage oxidative stress

BACKGROUND: Characterized by macrophage infiltration, renal inflammation during septic acute kidney injury (AKI) reveals a ubiquitous human health problem. Unfortunately, effective therapies with limited side effects are still lacking. This study is aiming to elucidate the role of Dimethyl fumarate...

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Autores principales: Zhou, Kejun, Xie, Mengyi, Yi, Shuli, Tang, Yun, Luo, Haojun, Xiao, Qiong, Xiao, Jun, Li, Yi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381931/
https://www.ncbi.nlm.nih.gov/pubmed/34402378
http://dx.doi.org/10.1080/0886022X.2021.1963774
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author Zhou, Kejun
Xie, Mengyi
Yi, Shuli
Tang, Yun
Luo, Haojun
Xiao, Qiong
Xiao, Jun
Li, Yi
author_facet Zhou, Kejun
Xie, Mengyi
Yi, Shuli
Tang, Yun
Luo, Haojun
Xiao, Qiong
Xiao, Jun
Li, Yi
author_sort Zhou, Kejun
collection PubMed
description BACKGROUND: Characterized by macrophage infiltration, renal inflammation during septic acute kidney injury (AKI) reveals a ubiquitous human health problem. Unfortunately, effective therapies with limited side effects are still lacking. This study is aiming to elucidate the role of Dimethyl fumarate (DMF) in macrophages against oxidative stress of septic AKI. METHODS: Balb/c mice were gavaged by 50 mg/kg DMF then injected with 10 mg/kg LPS by i.p. We examined LPS-induced renal dysfunction and histological features in murine kidneys. Raw264.7 macrophage cells were also treated with DMF and then induced by LPS. The mitotracker staining was used to follow mitochondria integrity by confocal microscopy. Flow cytometry measured the production of ROS by DCF-HDA and the expression of iNOS. Western blot detected the expression of Nrf-2 and Sirt1. Co-IP measured the interaction between Sirt1 and Nrf-2. Confocal microscopy observed the colocalization of Sirt1 and Nrf-2 in LPS-treated Raw264.7 macrophage cells. RESULTS: DMF ameliorated murine LPS nephritis with reduced blood urea nitrogen and serum creatinine, as well as decreased the histological alterations compared to the normal control. DMF significantly inhibited the expression of iNOS and reduced the production of nitrite in Raw264.7 cells following LPS treatment. Our study also revealed the role of DMF in protecting against intracellular ROS accumulation and mitochondria dysfunction in LPS-induced nephritis. DMF facilitated colocalization and interaction between Sirt1 and Nrf-2 in LPS-treated cells. CONCLUSIONS: This study showed that DMF alleviated LPS-induced nephritis, indicating protective effects of DMF on macrophage against oxidative stress induced by LPS potentially involving Nrf-2-mediated pathway.
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spelling pubmed-83819312021-08-24 Dimethyl fumarate ameliorates endotoxin-induced acute kidney injury against macrophage oxidative stress Zhou, Kejun Xie, Mengyi Yi, Shuli Tang, Yun Luo, Haojun Xiao, Qiong Xiao, Jun Li, Yi Ren Fail Laboratory Study BACKGROUND: Characterized by macrophage infiltration, renal inflammation during septic acute kidney injury (AKI) reveals a ubiquitous human health problem. Unfortunately, effective therapies with limited side effects are still lacking. This study is aiming to elucidate the role of Dimethyl fumarate (DMF) in macrophages against oxidative stress of septic AKI. METHODS: Balb/c mice were gavaged by 50 mg/kg DMF then injected with 10 mg/kg LPS by i.p. We examined LPS-induced renal dysfunction and histological features in murine kidneys. Raw264.7 macrophage cells were also treated with DMF and then induced by LPS. The mitotracker staining was used to follow mitochondria integrity by confocal microscopy. Flow cytometry measured the production of ROS by DCF-HDA and the expression of iNOS. Western blot detected the expression of Nrf-2 and Sirt1. Co-IP measured the interaction between Sirt1 and Nrf-2. Confocal microscopy observed the colocalization of Sirt1 and Nrf-2 in LPS-treated Raw264.7 macrophage cells. RESULTS: DMF ameliorated murine LPS nephritis with reduced blood urea nitrogen and serum creatinine, as well as decreased the histological alterations compared to the normal control. DMF significantly inhibited the expression of iNOS and reduced the production of nitrite in Raw264.7 cells following LPS treatment. Our study also revealed the role of DMF in protecting against intracellular ROS accumulation and mitochondria dysfunction in LPS-induced nephritis. DMF facilitated colocalization and interaction between Sirt1 and Nrf-2 in LPS-treated cells. CONCLUSIONS: This study showed that DMF alleviated LPS-induced nephritis, indicating protective effects of DMF on macrophage against oxidative stress induced by LPS potentially involving Nrf-2-mediated pathway. Taylor & Francis 2021-08-17 /pmc/articles/PMC8381931/ /pubmed/34402378 http://dx.doi.org/10.1080/0886022X.2021.1963774 Text en © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Laboratory Study
Zhou, Kejun
Xie, Mengyi
Yi, Shuli
Tang, Yun
Luo, Haojun
Xiao, Qiong
Xiao, Jun
Li, Yi
Dimethyl fumarate ameliorates endotoxin-induced acute kidney injury against macrophage oxidative stress
title Dimethyl fumarate ameliorates endotoxin-induced acute kidney injury against macrophage oxidative stress
title_full Dimethyl fumarate ameliorates endotoxin-induced acute kidney injury against macrophage oxidative stress
title_fullStr Dimethyl fumarate ameliorates endotoxin-induced acute kidney injury against macrophage oxidative stress
title_full_unstemmed Dimethyl fumarate ameliorates endotoxin-induced acute kidney injury against macrophage oxidative stress
title_short Dimethyl fumarate ameliorates endotoxin-induced acute kidney injury against macrophage oxidative stress
title_sort dimethyl fumarate ameliorates endotoxin-induced acute kidney injury against macrophage oxidative stress
topic Laboratory Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381931/
https://www.ncbi.nlm.nih.gov/pubmed/34402378
http://dx.doi.org/10.1080/0886022X.2021.1963774
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