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, 5mg/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.
Burn Center, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
Xiaochen
X
Qiu
Hengyu
H
Li
Hongtai
H
Tang
Yichao
Y
Jin
Wuquan
W
Li
YuSun
PingFeng
Xuejun
X
Sun
Zhaofan
Z
Xia
D055371:Acute Lung Injury / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D000280:Administration, Inhalation; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D053148:Caspase 3 / Q000378:metabolism; D016207:Cytokines / Q000032:analysis; D006859:Hydrogen / Q000008:administration & dosage*; D008070:Lipopolysaccharides / Q000008:administration & dosage; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D009195:Peroxidase / Q000378:metabolism; D011654:Pulmonary Edema / Q000188:drug therapy / Q000378:metabolism; D013482:Superoxide Dismutase / Q000032:analysis; D016896:Treatment Outcome; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
D000975:Antioxidants; C494827:Bax protein, mouse; D016207:Cytokines; D008070:Lipopolysaccharides; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; C002744:3-nitrotyrosine; D014443:Tyrosine; D008315:Malondialdehyde; D006859:Hydrogen; D009195:Peroxidase; D013482:Superoxide Dismutase; D053148:Caspase 3