Cargando…
Oxaloacetate acid ameliorates paraquat-induced acute lung injury by alleviating oxidative stress and mitochondrial dysfunction
Acute lung injury (ALI) is the primary cause of death among patients with acute paraquat (PQ) poisoning, whereby peroxidative damage is an important mechanism underlying PQ-induced lung injury. There is a lack of effective interventional drugs for patients with PQ poisoning. Oxaloacetic acid (OAA) p...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9606601/ https://www.ncbi.nlm.nih.gov/pubmed/36313362 http://dx.doi.org/10.3389/fphar.2022.1029775 |
_version_ | 1784818332643360768 |
---|---|
author | Li, Wenwen Li, Mengxuan Chen, Kaiyuan Tang, Yahui Yin, Ran Lan, Linhua Hong, Guangliang |
author_facet | Li, Wenwen Li, Mengxuan Chen, Kaiyuan Tang, Yahui Yin, Ran Lan, Linhua Hong, Guangliang |
author_sort | Li, Wenwen |
collection | PubMed |
description | Acute lung injury (ALI) is the primary cause of death among patients with acute paraquat (PQ) poisoning, whereby peroxidative damage is an important mechanism underlying PQ-induced lung injury. There is a lack of effective interventional drugs for patients with PQ poisoning. Oxaloacetic acid (OAA) participates in multiple in vivo metabolic processes, whereby it facilitates the clearance of reactive oxygen species (ROS) and improves mitochondrial function. The study aimed to assess the protective effects of OAA on PQ-induced ALI and elucidate the underlying molecular mechanism. Our data demonstrated that OAA treatment significantly alleviated PQ-induced ALI and improved the survival rate of PQ-poisoned mice, and also alleviated PQ-induced cellular oxidative stress and mitochondrial dysfunction. OAA-mediated alleviation of PQ-induced mitochondrial dysfunction depends on the following mechanisms which may explain the above findings: 1) OAA effectively cleared intracellular ROS, inhibited ROS accumulation, and mitochondrial depolarization; 2) OAA inhibited the downregulation of L-OPA1 and MFN2 caused by PQ and promoted a dynamic balance of mitochondrial fusion and fission, and 3) the expression of PGC-1α, TFAM, COX2, and COX4I1, increased significantly following OAA intervention which improved mitochondrial respiratory functions and promoted its biogenesis and energy metabolism in damaged cells. In conclusion, OAA effectively cleared ROS and improved mitochondrial dysfunction, thereby significantly improving ALI caused by PQ poisoning and the animal survival rate. Therefore, OAA may be a potential drug for the treatment of PQ poisoning. |
format | Online Article Text |
id | pubmed-9606601 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-96066012022-10-28 Oxaloacetate acid ameliorates paraquat-induced acute lung injury by alleviating oxidative stress and mitochondrial dysfunction Li, Wenwen Li, Mengxuan Chen, Kaiyuan Tang, Yahui Yin, Ran Lan, Linhua Hong, Guangliang Front Pharmacol Pharmacology Acute lung injury (ALI) is the primary cause of death among patients with acute paraquat (PQ) poisoning, whereby peroxidative damage is an important mechanism underlying PQ-induced lung injury. There is a lack of effective interventional drugs for patients with PQ poisoning. Oxaloacetic acid (OAA) participates in multiple in vivo metabolic processes, whereby it facilitates the clearance of reactive oxygen species (ROS) and improves mitochondrial function. The study aimed to assess the protective effects of OAA on PQ-induced ALI and elucidate the underlying molecular mechanism. Our data demonstrated that OAA treatment significantly alleviated PQ-induced ALI and improved the survival rate of PQ-poisoned mice, and also alleviated PQ-induced cellular oxidative stress and mitochondrial dysfunction. OAA-mediated alleviation of PQ-induced mitochondrial dysfunction depends on the following mechanisms which may explain the above findings: 1) OAA effectively cleared intracellular ROS, inhibited ROS accumulation, and mitochondrial depolarization; 2) OAA inhibited the downregulation of L-OPA1 and MFN2 caused by PQ and promoted a dynamic balance of mitochondrial fusion and fission, and 3) the expression of PGC-1α, TFAM, COX2, and COX4I1, increased significantly following OAA intervention which improved mitochondrial respiratory functions and promoted its biogenesis and energy metabolism in damaged cells. In conclusion, OAA effectively cleared ROS and improved mitochondrial dysfunction, thereby significantly improving ALI caused by PQ poisoning and the animal survival rate. Therefore, OAA may be a potential drug for the treatment of PQ poisoning. Frontiers Media S.A. 2022-10-13 /pmc/articles/PMC9606601/ /pubmed/36313362 http://dx.doi.org/10.3389/fphar.2022.1029775 Text en Copyright © 2022 Li, Li, Chen, Tang, Yin, Lan and Hong. 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 Li, Wenwen Li, Mengxuan Chen, Kaiyuan Tang, Yahui Yin, Ran Lan, Linhua Hong, Guangliang Oxaloacetate acid ameliorates paraquat-induced acute lung injury by alleviating oxidative stress and mitochondrial dysfunction |
title | Oxaloacetate acid ameliorates paraquat-induced acute lung injury by alleviating oxidative stress and mitochondrial dysfunction |
title_full | Oxaloacetate acid ameliorates paraquat-induced acute lung injury by alleviating oxidative stress and mitochondrial dysfunction |
title_fullStr | Oxaloacetate acid ameliorates paraquat-induced acute lung injury by alleviating oxidative stress and mitochondrial dysfunction |
title_full_unstemmed | Oxaloacetate acid ameliorates paraquat-induced acute lung injury by alleviating oxidative stress and mitochondrial dysfunction |
title_short | Oxaloacetate acid ameliorates paraquat-induced acute lung injury by alleviating oxidative stress and mitochondrial dysfunction |
title_sort | oxaloacetate acid ameliorates paraquat-induced acute lung injury by alleviating oxidative stress and mitochondrial dysfunction |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9606601/ https://www.ncbi.nlm.nih.gov/pubmed/36313362 http://dx.doi.org/10.3389/fphar.2022.1029775 |
work_keys_str_mv | AT liwenwen oxaloacetateacidamelioratesparaquatinducedacutelunginjurybyalleviatingoxidativestressandmitochondrialdysfunction AT limengxuan oxaloacetateacidamelioratesparaquatinducedacutelunginjurybyalleviatingoxidativestressandmitochondrialdysfunction AT chenkaiyuan oxaloacetateacidamelioratesparaquatinducedacutelunginjurybyalleviatingoxidativestressandmitochondrialdysfunction AT tangyahui oxaloacetateacidamelioratesparaquatinducedacutelunginjurybyalleviatingoxidativestressandmitochondrialdysfunction AT yinran oxaloacetateacidamelioratesparaquatinducedacutelunginjurybyalleviatingoxidativestressandmitochondrialdysfunction AT lanlinhua oxaloacetateacidamelioratesparaquatinducedacutelunginjurybyalleviatingoxidativestressandmitochondrialdysfunction AT hongguangliang oxaloacetateacidamelioratesparaquatinducedacutelunginjurybyalleviatingoxidativestressandmitochondrialdysfunction |