Hydrogen inhalation ameliorates lipopolysaccharide-induced acute lung injury in mice

Acute lung injury (ALI) is a serious illness, the incidence and mortality of which are very high. Free radicals, such as hydroxyl radicals (OH) and peroxynitrite (ONOO−), are considered to be the final causative molecules in the pathogenesis of ALI. Hydrogen, a new antioxidant, can selectively reduce OH and ONOO−. In the present study, we investigated the hypothesis that hydrogen inhalation could ameliorate ALI induced by intra-tracheal lipopolysaccharide (LPS, 5 mg/kg body weight). Mice were randomized into three groups: sham group (physiological saline + 2% hydrogen mixed gas), control group (LPS + normal air) and experiment group (LPS + 2% hydrogen mixed gas). Bronchoalveolar lavage fluid (BALF) was performed to determine the total protein concentrations and pro-inflammatory cytokines. Lung tissues were assayed for oxidative stress variables, wet/dry (W/D) ratio, histological, immunohistochemistry and Western blotting examinations. Our experiments exhibited that hydrogen improved the survival rate of mice and induced a decrease in lung W/D ratio. In addition, hydrogen decreased malonaldehyde and nitrotyrosine content, inhibited myeloperoxidase and maintained superoxide dismutase activity in lung tissues and associated with a decrease in the expression of TNF-α, IL-1β, IL-6 and total protein concentrations in the BALF. Hydrogen further attenuated histopathological alterations and mitigated lung cell apoptosis. Importantly, hydrogen inhibited the activation of P-JNK, and also reversed changes in Bax, Bcl-xl and caspase-3. In conclusion, our data demonstrated that hydrogen inhalation ameliorated LPS-induced ALI and it may be exerting its protective role by preventing the activation of ROS-JNK-caspase-3 pathway.

► Hydrogen inhalation ameliorated the LPS-induced oxidative stress. ► Hydrogen prevented the release of pro-inflammatory molecules and attenuated P-JNK levels. ► Hydrogen inhibited lung cell apoptosis through inhibiting the caspase-3 and Bax and preventing the decrease of Bcl-xl. ► Hydrogen may be exerting its protective role by preventing the activation of ROS-JNK-caspase-3 pathway