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Metformin mitigates gas explosion-induced blast lung injuries through AMPK-mediated energy metabolism and NOX2-related oxidation pathway in rats
Gas explosions are a recurrent event in coal mining that cause severe pulmonary damage due to shock waves, and there is currently no effective targeted treatment. To illustrate the mechanism of gas explosion-induced lung injury and to explore strategies for blast lung injury (BLI) treatment, the pre...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9257965/ https://www.ncbi.nlm.nih.gov/pubmed/35837050 http://dx.doi.org/10.3892/etm.2022.11456 |
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author | Zhang, Miao Sun, Yunzhe Ding, Chunjie Hong, Shan Li, Ning Guan, Yi Zhang, Lin Dong, Xinwen Cao, Jia Yao, Wu Ren, Wenjie Yao, Sanqiao |
author_facet | Zhang, Miao Sun, Yunzhe Ding, Chunjie Hong, Shan Li, Ning Guan, Yi Zhang, Lin Dong, Xinwen Cao, Jia Yao, Wu Ren, Wenjie Yao, Sanqiao |
author_sort | Zhang, Miao |
collection | PubMed |
description | Gas explosions are a recurrent event in coal mining that cause severe pulmonary damage due to shock waves, and there is currently no effective targeted treatment. To illustrate the mechanism of gas explosion-induced lung injury and to explore strategies for blast lung injury (BLI) treatment, the present study used a BLI rat model and supplementation with metformin (MET), an AMP-activated protein kinase (AMPK) activator, at a dose of 10 mg/kg body weight by intraperitoneal injection. Protein expression levels were detected by western blotting. Significantly decreased expression of phosphorylated (p)-AMPK, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) and metabolic activity were observed in the BLI group compared with those in the control group. However, the mitochondrial stability, metabolic activity and expression of p-AMPK and PGC1α were elevated following MET treatment. These results suggested that MET could attenuate gas explosion-induced BLI by improving mitochondrial homeostasis. Meanwhile, high expression of nicotinamide adenine dinucleotide phosphate oxidase (NOX2) and low expression of catalase (CAT) were observed in the BLI group. The expression levels of NOX2 and CAT were restored in the BLI + MET group relative to changes in the BLI group, and the accumulation of oxidative stress was successfully reversed following MET treatment. Overall, these findings revealed that MET could alleviate BLI by activating the AMPK/PGC1α pathway and inhibiting oxidative stress caused by NOX2 activation. |
format | Online Article Text |
id | pubmed-9257965 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-92579652022-07-13 Metformin mitigates gas explosion-induced blast lung injuries through AMPK-mediated energy metabolism and NOX2-related oxidation pathway in rats Zhang, Miao Sun, Yunzhe Ding, Chunjie Hong, Shan Li, Ning Guan, Yi Zhang, Lin Dong, Xinwen Cao, Jia Yao, Wu Ren, Wenjie Yao, Sanqiao Exp Ther Med Articles Gas explosions are a recurrent event in coal mining that cause severe pulmonary damage due to shock waves, and there is currently no effective targeted treatment. To illustrate the mechanism of gas explosion-induced lung injury and to explore strategies for blast lung injury (BLI) treatment, the present study used a BLI rat model and supplementation with metformin (MET), an AMP-activated protein kinase (AMPK) activator, at a dose of 10 mg/kg body weight by intraperitoneal injection. Protein expression levels were detected by western blotting. Significantly decreased expression of phosphorylated (p)-AMPK, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) and metabolic activity were observed in the BLI group compared with those in the control group. However, the mitochondrial stability, metabolic activity and expression of p-AMPK and PGC1α were elevated following MET treatment. These results suggested that MET could attenuate gas explosion-induced BLI by improving mitochondrial homeostasis. Meanwhile, high expression of nicotinamide adenine dinucleotide phosphate oxidase (NOX2) and low expression of catalase (CAT) were observed in the BLI group. The expression levels of NOX2 and CAT were restored in the BLI + MET group relative to changes in the BLI group, and the accumulation of oxidative stress was successfully reversed following MET treatment. Overall, these findings revealed that MET could alleviate BLI by activating the AMPK/PGC1α pathway and inhibiting oxidative stress caused by NOX2 activation. D.A. Spandidos 2022-06-20 /pmc/articles/PMC9257965/ /pubmed/35837050 http://dx.doi.org/10.3892/etm.2022.11456 Text en Copyright: © Zhang et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Zhang, Miao Sun, Yunzhe Ding, Chunjie Hong, Shan Li, Ning Guan, Yi Zhang, Lin Dong, Xinwen Cao, Jia Yao, Wu Ren, Wenjie Yao, Sanqiao Metformin mitigates gas explosion-induced blast lung injuries through AMPK-mediated energy metabolism and NOX2-related oxidation pathway in rats |
title | Metformin mitigates gas explosion-induced blast lung injuries through AMPK-mediated energy metabolism and NOX2-related oxidation pathway in rats |
title_full | Metformin mitigates gas explosion-induced blast lung injuries through AMPK-mediated energy metabolism and NOX2-related oxidation pathway in rats |
title_fullStr | Metformin mitigates gas explosion-induced blast lung injuries through AMPK-mediated energy metabolism and NOX2-related oxidation pathway in rats |
title_full_unstemmed | Metformin mitigates gas explosion-induced blast lung injuries through AMPK-mediated energy metabolism and NOX2-related oxidation pathway in rats |
title_short | Metformin mitigates gas explosion-induced blast lung injuries through AMPK-mediated energy metabolism and NOX2-related oxidation pathway in rats |
title_sort | metformin mitigates gas explosion-induced blast lung injuries through ampk-mediated energy metabolism and nox2-related oxidation pathway in rats |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9257965/ https://www.ncbi.nlm.nih.gov/pubmed/35837050 http://dx.doi.org/10.3892/etm.2022.11456 |
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