Combination therapy of molecular hydrogen and hyperoxia improves survival rate and organ damage in a zymosan-induced generalized inflammation model.

Abstract

Multiple organ dysfunction syndrome (MODS) represents a critical cause of death in severely ill patients. This animal study examined the effects of inhaled 2% hydrogen gas (H2), 98% hyperoxia, and their combination in a zymosan (ZY)-induced generalized inflammation mouse model. Fourteen-day survival rates rose from 20% in untreated ZY-challenged mice to 70% with H2 alone and 60% with hyperoxia alone, while the combined regimen achieved 100% survival. Serum markers of hepatic and renal injury—including AST, ALT, blood urea nitrogen, and creatinine—along with histopathological scores for lung, liver, and kidney, were all reduced most substantially by the combination. Mechanistically, the combined approach decreased serum 8-iso-prostaglandin F2α (an oxidative stress marker), elevated superoxide dismutase activity, and lowered the pro-inflammatory mediators HMGB1 and TNF-α. These findings indicate that concurrent H2 and hyperoxia inhalation provides additive protection against inflammation-driven multi-organ damage beyond what either intervention achieves individually.

Mechanism

H2 selectively scavenges reactive oxygen species, counteracting the oxidative burden imposed by hyperoxia. This is accompanied by elevated superoxide dismutase activity and suppression of pro-inflammatory cytokines HMGB1 and TNF-α, collectively reducing multi-organ injury.