Oxidative stress in ARDS: mechanisms and therapeutic potential

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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Main Authors: Fengyun Wang, Ruiqi Ge, Yun Cai, Mingrui Zhao, Zhen Fang, Jingguo Li, Chengzhi Xie, Mei Wang, Wanyue Li, Xiaozhi Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Pharmacology
Subjects:
acute respiratory distress syndrome (ARDS)
acute lung injury (ALI)
oxidative stress
reactive oxygen species (ROS)
inflammation
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2025.1603287/full
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Summary: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.
ISSN:1663-9812

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