Molecular hydrogen ameliorates lipopolysaccharide-induced acute lung injury in mice through reducing inflammation and apoptosis.

Abstract

Acute lung injury (ALI) remains a critical contributor to mortality in intensive care settings. This mouse study examined the effects of 2% H2 gas inhalation (administered for 1 hour at 1 and 6 hours post-LPS challenge) and intraperitoneal hydrogen-rich saline (10 mL/kg) in an intratracheal LPS-induced ALI model. Both delivery routes improved histopathological scores, wet-to-dry weight ratio, oxygenation index (PaO2/FiO2), and total protein levels in bronchoalveolar lavage fluid (BALF). H2 suppressed both early and late pulmonary NF-κB activation. Apoptosis was reduced, as indicated by fewer TUNEL-positive cells and lower caspase-3 activity. Neutrophil infiltration, myeloperoxidase activity, and concentrations of proinflammatory cytokines (TNF-α, IL-1β, IL-6, HMGB1) and chemokines (KC, MIP-1α, MIP-2, MCP-1) in BALF were all markedly decreased. These findings indicate that molecular hydrogen mitigates LPS-induced ALI by attenuating NF-κB-mediated inflammatory and apoptotic responses.

Mechanism

H2 suppresses both early and late NF-κB activation in lung tissue, thereby reducing proinflammatory cytokine and chemokine production, neutrophil recruitment, and caspase-3-dependent apoptosis in LPS-challenged mice.