Oxidative stress in ARDS: mechanisms and therapeutic potential
Acute respiratory distress syndrome (ARDS) is a life-threatening condition characterized by acute lung inflammation, increased vascular permeability, and hypoxemic respiratory failure. Oxidative stress, driven by excessive reactive oxygen species (ROS), is a key contributor to ARDS pathogenesis, cau...
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Frontiers Media S.A.
2025-06-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1603287/full |
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| author | Fengyun Wang Ruiqi Ge Yun Cai Mingrui Zhao Zhen Fang Jingguo Li Chengzhi Xie Mei Wang Wanyue Li Xiaozhi Wang |
| author_facet | Fengyun Wang Ruiqi Ge Yun Cai Mingrui Zhao Zhen Fang Jingguo Li Chengzhi Xie Mei Wang Wanyue Li Xiaozhi Wang |
| author_sort | Fengyun Wang |
| collection | DOAJ |
| description | Acute respiratory distress syndrome (ARDS) is a life-threatening condition characterized by acute lung inflammation, increased vascular permeability, and hypoxemic respiratory failure. Oxidative stress, driven by excessive reactive oxygen species (ROS), is a key contributor to ARDS pathogenesis, causing cellular damage, inflammation, and alveolar-capillary barrier disruption. This review elucidates the mechanisms of oxidative stress in ARDS, focusing on ROS production via NADPH oxidase (NOX) and mitochondria, which activate pathways like NF-κB and MAPK, promoting pro-inflammatory cytokine release. ROS-induced lipid and protein peroxidation, endothelial dysfunction, and programmed cell death (PCD), including apoptosis, pyroptosis, and ferroptosis, exacerbate lung injury. In COVID-19-related ARDS, SARS-CoV-2 spike protein amplifies mitochondrial ROS, worsening outcomes. Antioxidant therapies falter due to non-specific ROS suppression, patient heterogeneity (e.g., GSTP1 polymorphisms), and poor bioavailability. We propose a model where oxidative stress drives ARDS stages—early alveolar injury and late systemic dysfunction—suggesting targeted therapies like endothelial-specific nanoparticles or ferroptosis inhibitors. Precision medicine using biomarkers (e.g., mtDNA) and gender-specific approaches (e.g., estrogen-Nrf2 regulation) could enhance outcomes. This review bridges mechanistic gaps, critiques therapeutic failures, and advocates novel strategies like mitochondrial-targeted therapies to improve ARDS management. |
| format | Article |
| id | doaj-art-2f24599cf9dd4d1e8f41b45d70c6584e |
| institution | OA Journals |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-2f24599cf9dd4d1e8f41b45d70c6584e2025-08-20T02:24:14ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-06-011610.3389/fphar.2025.16032871603287Oxidative stress in ARDS: mechanisms and therapeutic potentialFengyun Wang0Ruiqi Ge1Yun Cai2Mingrui Zhao3Zhen Fang4Jingguo Li5Chengzhi Xie6Mei Wang7Wanyue Li8Xiaozhi Wang9Department of Critical Care Medicine, Second Affiliated Hospital of Hainan Medical University, Haikou, ChinaDepartment of Critical Care Medicine, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, ChinaDepartment of Critical Care Medicine, Second Affiliated Hospital of Hainan Medical University, Haikou, ChinaDepartment of Critical Care Medicine, Second Affiliated Hospital of Hainan Medical University, Haikou, ChinaDepartment of Critical Care Medicine, Second Affiliated Hospital of Hainan Medical University, Haikou, ChinaDepartment of Critical Care Medicine, Second Affiliated Hospital of Hainan Medical University, Haikou, ChinaDepartment of Critical Care Medicine, Second Affiliated Hospital of Hainan Medical University, Haikou, ChinaDepartment of Critical Care Medicine, Second Affiliated Hospital of Hainan Medical University, Haikou, ChinaDepartment of Critical Care Medicine, Second Affiliated Hospital of Hainan Medical University, Haikou, ChinaDepartment of Critical Care Medicine, Second Affiliated Hospital of Hainan Medical University, Haikou, ChinaAcute respiratory distress syndrome (ARDS) is a life-threatening condition characterized by acute lung inflammation, increased vascular permeability, and hypoxemic respiratory failure. Oxidative stress, driven by excessive reactive oxygen species (ROS), is a key contributor to ARDS pathogenesis, causing cellular damage, inflammation, and alveolar-capillary barrier disruption. This review elucidates the mechanisms of oxidative stress in ARDS, focusing on ROS production via NADPH oxidase (NOX) and mitochondria, which activate pathways like NF-κB and MAPK, promoting pro-inflammatory cytokine release. ROS-induced lipid and protein peroxidation, endothelial dysfunction, and programmed cell death (PCD), including apoptosis, pyroptosis, and ferroptosis, exacerbate lung injury. In COVID-19-related ARDS, SARS-CoV-2 spike protein amplifies mitochondrial ROS, worsening outcomes. Antioxidant therapies falter due to non-specific ROS suppression, patient heterogeneity (e.g., GSTP1 polymorphisms), and poor bioavailability. We propose a model where oxidative stress drives ARDS stages—early alveolar injury and late systemic dysfunction—suggesting targeted therapies like endothelial-specific nanoparticles or ferroptosis inhibitors. Precision medicine using biomarkers (e.g., mtDNA) and gender-specific approaches (e.g., estrogen-Nrf2 regulation) could enhance outcomes. This review bridges mechanistic gaps, critiques therapeutic failures, and advocates novel strategies like mitochondrial-targeted therapies to improve ARDS management.https://www.frontiersin.org/articles/10.3389/fphar.2025.1603287/fullacute respiratory distress syndrome (ARDS)acute lung injury (ALI)oxidative stressreactive oxygen species (ROS)inflammation |
| spellingShingle | Fengyun Wang Ruiqi Ge Yun Cai Mingrui Zhao Zhen Fang Jingguo Li Chengzhi Xie Mei Wang Wanyue Li Xiaozhi Wang Oxidative stress in ARDS: mechanisms and therapeutic potential Frontiers in Pharmacology acute respiratory distress syndrome (ARDS) acute lung injury (ALI) oxidative stress reactive oxygen species (ROS) inflammation |
| title | Oxidative stress in ARDS: mechanisms and therapeutic potential |
| title_full | Oxidative stress in ARDS: mechanisms and therapeutic potential |
| title_fullStr | Oxidative stress in ARDS: mechanisms and therapeutic potential |
| title_full_unstemmed | Oxidative stress in ARDS: mechanisms and therapeutic potential |
| title_short | Oxidative stress in ARDS: mechanisms and therapeutic potential |
| title_sort | oxidative stress in ards mechanisms and therapeutic potential |
| topic | acute respiratory distress syndrome (ARDS) acute lung injury (ALI) oxidative stress reactive oxygen species (ROS) inflammation |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1603287/full |
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