MOLECULAR HYDROGEN AMELIORATES LIPOPOLYSACCHARIDE-INDUCED ACUTE LUNG INJURY IN MICE THROUGH REDUCING INFLAMMATION AND APOPTOSIS

Acute lung injury (ALI) is still a leading cause of morbidity and mortality in critically ill patients. Recently, our and other studies have found that hydrogen gas (H-2) treatment can ameliorate the lung injury induced by sepsis, ventilator, hyperoxia, and ischemia-reperfusion. However, the molecular mechanisms by which H-2 ameliorates lung injury remain unclear. In the current study, we investigated whether H-2 or hydrogen-rich saline (HS) could exert protective effects in a mouse model of ALI induced by intratracheal administration of lipopolysaccharide (LPS) via inhibiting the nuclear factor kappa B (NF-kappa B) signaling pathway-mediated inflammation and apoptosis. Two percent of H-2 was inhaled for 1 h beginning at 1 and 6 h after LPS administration, respectively. We found that LPS-challenged mice exhibited significant lung injury characterized by the deterioration of histopathology and histologic scores, wet-to-dry weight ratio, and oxygenation index (PaO2/FIO2), as well as total protein in the bronchoalveolar lavage fluid (BALF), which was attenuated by H-2 treatment. Hydrogen gas treatment inhibited LPS-induced pulmonary early and late NF-kappa B activation. Moreover, H-2 treatment dramatically prevented the LPS-induced pulmonary cell apoptosis in LPS-challenged mice, as reflected by the decrease in TUNEL (deoxynucleotidyl transferase dUTP nick end labeling) staining-positive cells and caspase 3 activity. Furthermore, H-2 treatment markedly attenuated LPS-induced lung neutrophil recruitment and inflammation, as evidenced by downregulation of lung myeloperoxidase activity, total cells, and polymorphonuclear neutrophils in BALF, as well as proinflammatory cytokines (tumor necrosis factor alpha, interleukin 1 beta, interleukin 6, and high-mobility group box 1) and chemokines (keratinocyte-derived chemokine, macrophage inflammatory protein [MIP] 1 alpha, MIP-2, and monocyte chemoattractant protein 1) in BALF. In addition, i.p. injection of 10 mL/kg hydrogen-rich saline also significantly attenuated the LPS-induced ALI. Collectively, these results demonstrate that molecular hydrogen treatment ameliorates LPS-induced ALI through reducing lung inflammation and apoptosis, which may be associated with the decreased NF-kappa B activity. Hydrogen gas may be useful as a novel therapy to treat ALI.