Oxidative stress in ARDS: mechanisms and therapeutic potential

Area of Science:

• * Focuses on the critical role of oxidative stress in the pathogenesis of acute respiratory distress syndrome (ARDS).

Background:

• * ARDS involves acute lung inflammation, vascular permeability, and hypoxemic respiratory failure.
• * Oxidative stress, from excessive reactive oxygen species (ROS), is a major driver of ARDS, causing cellular damage and barrier disruption.

Purpose of the Study:

• * To elucidate mechanisms of oxidative stress in ARDS, including ROS production and signaling pathways.
• * To critique current antioxidant therapy failures and propose novel therapeutic strategies.

Main Methods:

• * Review of mechanisms of ROS production (NADPH oxidase, mitochondria) and downstream signaling (NF-κB, MAPK).
• * Examination of ROS-induced cellular damage, including lipid peroxidation, endothelial dysfunction, and programmed cell death (apoptosis, pyroptosis, ferroptosis).
• * Analysis of ARDS exacerbation in COVID-19 and limitations of current antioxidant therapies.

Main Results:

• * ROS activates inflammatory pathways and exacerbates lung injury through various cell death mechanisms.
• * SARS-CoV-2 spike protein amplifies mitochondrial ROS, worsening COVID-19 ARDS.
• * Antioxidant therapies are limited by non-specific ROS suppression, patient heterogeneity, and poor bioavailability.

Conclusions:

• * Oxidative stress drives distinct ARDS stages, suggesting stage-specific targeted therapies.
• * Novel strategies include endothelial-specific nanoparticles, ferroptosis inhibitors, and mitochondrial-targeted therapies.
• * Precision medicine, utilizing biomarkers and gender-specific approaches, can improve ARDS outcomes.