Combating Oxidative Stress and Inflammation in COVID-19 by Molecular Hydrogen Therapy: Mechanisms and Perspectives.

Abstract

COVID-19, caused by SARS-CoV-2 infection targeting alveolar type II pneumocytes, triggers pathological cascades including heightened inflammation, oxidative stress, and apoptosis, ultimately leading to impaired gas exchange and multiorgan failure. This review systematically examines the antioxidative, anti-inflammatory, and antiapoptotic properties of molecular hydrogen (H2) as a candidate intervention for COVID-19-related complications. Due to its small size and nonpolar nature, H2 readily crosses cell membranes and reaches intracellular organelles. Evidence indicates that H2 suppresses NF-κB-mediated inflammatory signaling while activating the Nrf2/Keap1 antioxidant pathway, and also supports mitochondrial function and cellular bioenergetics. Although preclinical and clinical data across multiple disease contexts, including COVID-19, suggest beneficial outcomes, the precise primary mechanisms and definitive clinical efficacy remain to be fully established, underscoring the need for further rigorous investigation.

Mechanism

H2 penetrates cell membranes and organelles due to its small size and nonpolarity, suppresses NF-κB inflammatory signaling, activates the Nrf2/Keap1 antioxidant pathway, and improves mitochondrial function and cellular bioenergetics.