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 (H₂) treatment can ameliorate the
lung injury induced by
sepsis,
ventilator,
hyperoxia, and
ischemia-reperfusion. However, the molecular mechanisms by which H₂ ameliorates
lung injury remain unclear. In the current study, we investigated whether H₂ 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 κB (NF-κB) signaling pathway-mediated
inflammation and apoptosis. Two percent of H₂ 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 H₂ treatment.
Hydrogen gas treatment inhibited LPS-induced pulmonary early and late NF-κB activation. Moreover, H₂ 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, H₂ 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 α,
interleukin 1β,
interleukin 6, and high-mobility group box 1) and
chemokines (keratinocyte-derived
chemokine,
macrophage inflammatory protein [MIP] 1α, 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-κB activity.
Hydrogen gas may be useful as a novel
therapy to treat ALI. munosorbent assay; H₂-
hydrogen gas; HMGB1-high-mobility group box 1; HS-
hydrogen-rich saline; i.t.-intratracheal; KC-keratinocyte-derived
chemokine; LPS-
lipopolysaccharide; MCP-1-monocyte
chemoattractant protein 1; MIP-1α-macrophage inflammatory
protein 1α; MIP-2-macrophage inflammatory
protein 2; MPO-
myeloperoxidase; PBS-
phosphate-buffered saline; PMNs-polymorphonuclear neutrophils; TUNEL-
deoxynucleotidyl transferase dUTP nick end labeling; W/D-wet-to-dry.