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Urolithin A (UA) attenuates ferroptosis in LPS-induced acute lung injury in mice by upregulating Keap1-Nrf2/HO-1 signaling pathway

Acute lung injury (ALI) is a life-threatening disease with high incidence and mortality rates. Urolithin A (UA) is a pomegranate intestinal flora metabolite with anti-inflammatory, antioxidant, and anti-aging properties. Ferroptosis is a critical factor in lipopolysaccharide (LPS)-induced acute lung...

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Autores principales: Lou, Lejing, Wang, Min, He, Jingjing, Yang, Song, Meng, Fanxi, Wang, Shijia, Jin, Xiao, Cai, Jihao, Cai, Chang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10034769/
https://www.ncbi.nlm.nih.gov/pubmed/36969874
http://dx.doi.org/10.3389/fphar.2023.1067402
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author Lou, Lejing
Wang, Min
He, Jingjing
Yang, Song
Meng, Fanxi
Wang, Shijia
Jin, Xiao
Cai, Jihao
Cai, Chang
author_facet Lou, Lejing
Wang, Min
He, Jingjing
Yang, Song
Meng, Fanxi
Wang, Shijia
Jin, Xiao
Cai, Jihao
Cai, Chang
author_sort Lou, Lejing
collection PubMed
description Acute lung injury (ALI) is a life-threatening disease with high incidence and mortality rates. Urolithin A (UA) is a pomegranate intestinal flora metabolite with anti-inflammatory, antioxidant, and anti-aging properties. Ferroptosis is a critical factor in lipopolysaccharide (LPS)-induced acute lung injury (ALI). However, the link between UA and ferroptosis is unknown. The purpose of this research was to look into the role of UA in regulating LPS-induced ferroptosis in ALI. The current study used LPS to injure two models, one BEAS-2B cell injury model and one ALI mouse model. UA effectively alleviated LPS-induced ALI compared to the LPS group by lowering in vivo lung wet/dry weight ratio, reactive oxygen species, and malondialdehyde production, as well as superoxide dismutase, catalase, and glutathione depletion. Furthermore, by increasing GPX4 and SLC7A11 expression and decreasing Fe(2+) levels, lung histopathological damage, inflammatory cytokine secretion, and ferroptosis levels can be significantly reduced. The Keap1-Nrf2/HO-1 pathway was upregulated by UA, which inhibited LPS-induced ALI and ferroptosis. ML385 inhibited UA’s protective effect against LPS-induced ALI. These findings suggested that UA could be a novel potential therapeutic target for ALI.
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spelling pubmed-100347692023-03-24 Urolithin A (UA) attenuates ferroptosis in LPS-induced acute lung injury in mice by upregulating Keap1-Nrf2/HO-1 signaling pathway Lou, Lejing Wang, Min He, Jingjing Yang, Song Meng, Fanxi Wang, Shijia Jin, Xiao Cai, Jihao Cai, Chang Front Pharmacol Pharmacology Acute lung injury (ALI) is a life-threatening disease with high incidence and mortality rates. Urolithin A (UA) is a pomegranate intestinal flora metabolite with anti-inflammatory, antioxidant, and anti-aging properties. Ferroptosis is a critical factor in lipopolysaccharide (LPS)-induced acute lung injury (ALI). However, the link between UA and ferroptosis is unknown. The purpose of this research was to look into the role of UA in regulating LPS-induced ferroptosis in ALI. The current study used LPS to injure two models, one BEAS-2B cell injury model and one ALI mouse model. UA effectively alleviated LPS-induced ALI compared to the LPS group by lowering in vivo lung wet/dry weight ratio, reactive oxygen species, and malondialdehyde production, as well as superoxide dismutase, catalase, and glutathione depletion. Furthermore, by increasing GPX4 and SLC7A11 expression and decreasing Fe(2+) levels, lung histopathological damage, inflammatory cytokine secretion, and ferroptosis levels can be significantly reduced. The Keap1-Nrf2/HO-1 pathway was upregulated by UA, which inhibited LPS-induced ALI and ferroptosis. ML385 inhibited UA’s protective effect against LPS-induced ALI. These findings suggested that UA could be a novel potential therapeutic target for ALI. Frontiers Media S.A. 2023-03-09 /pmc/articles/PMC10034769/ /pubmed/36969874 http://dx.doi.org/10.3389/fphar.2023.1067402 Text en Copyright © 2023 Lou, Wang, He, Yang, Meng, Wang, Jin, Cai and Cai. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Lou, Lejing
Wang, Min
He, Jingjing
Yang, Song
Meng, Fanxi
Wang, Shijia
Jin, Xiao
Cai, Jihao
Cai, Chang
Urolithin A (UA) attenuates ferroptosis in LPS-induced acute lung injury in mice by upregulating Keap1-Nrf2/HO-1 signaling pathway
title Urolithin A (UA) attenuates ferroptosis in LPS-induced acute lung injury in mice by upregulating Keap1-Nrf2/HO-1 signaling pathway
title_full Urolithin A (UA) attenuates ferroptosis in LPS-induced acute lung injury in mice by upregulating Keap1-Nrf2/HO-1 signaling pathway
title_fullStr Urolithin A (UA) attenuates ferroptosis in LPS-induced acute lung injury in mice by upregulating Keap1-Nrf2/HO-1 signaling pathway
title_full_unstemmed Urolithin A (UA) attenuates ferroptosis in LPS-induced acute lung injury in mice by upregulating Keap1-Nrf2/HO-1 signaling pathway
title_short Urolithin A (UA) attenuates ferroptosis in LPS-induced acute lung injury in mice by upregulating Keap1-Nrf2/HO-1 signaling pathway
title_sort urolithin a (ua) attenuates ferroptosis in lps-induced acute lung injury in mice by upregulating keap1-nrf2/ho-1 signaling pathway
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10034769/
https://www.ncbi.nlm.nih.gov/pubmed/36969874
http://dx.doi.org/10.3389/fphar.2023.1067402
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