BACKGROUND

Chronic inflammation and oxidant/antioxidant imbalance are two main pathological features associated with lipopolysaccharide (LPS)-induced acute lung injury (ALI). The following study investigated the protective role of hydrogen (H), a gaseous molecule without known toxicity, in LPS-induced lung injury in mice and explored its potential molecular mechanisms.

METHODS

Mice were randomly divided into three groups: H control group, LPS group, and LPS + H group. The mice were euthanized at the indicated time points, and the specimens were collected. The 72 h survival rates, cytokines contents, pathological changes, expression of Toll-like receptor 4 (TLR4), and oxidative stress indicators were analyzed. Moreover, under different culture conditions, RAW 264.7 mouse macrophages were used to investigate the potential molecular mechanisms of H in vitro. Cells were divided into the following groups: PBS group, LPS group, and LPS + H group. The cell viability, intracellular ROS, cytokines, and expression of TLR4 and nuclear factor kappa-B (NF-κB) were observed.

RESULTS

Hydrogen inhalation increased the survival rate to 80%, reduced LPS-induced lung damage, and decreased inflammatory cytokine release in LPS mice. Besides, H showed remarked anti-oxidative activity to reduce the MDA and NO contents in the lung. In vitro data further indicated that H down-regulates the levels of ROS, NO, TNF-α, IL-6, and IL-1β in LPS-stimulated macrophages and inhibits the expression of TLR4 and the activation of nuclear factor kappa-B (NF-κB).

CONCLUSION

Hydrogen gas alleviates lipopolysaccharide-induced acute lung injury and inflammatory response most probably through the TLR4-NF-κB pathway.