Melatonin prevents lung injury induced by hepatic ischemia-reperfusion through anti-inflammatory and anti-apoptosis effects.
Melatonin is a free radical scavenger and broad-spectrum antioxidant with immunomodulatory effects. The objective of the study is to investigate the effects of melatonin in hepatic ischemia/reperfusion (I/R) induced lung injury and explore its underlying mechanisms. Hepatic I/R injury was induced via portal vein and hepatic artery occlusion for 30min followed by 3-h reperfusion. Male Sprague-Dawley rats were divided into three groups: sham, I/R+ Vehicle and I/R+melatonin. Melatonin (10mg/kg) or vehicle was injected intravenously 15min before ischemia and 10min before reperfusion. The histology of the liver and lung, plasma aminotransferase and cytokine secretion, and apoptosis in the lung were evaluated. The phosphorylation of JNK, p38, and NF-ƙB and Nrf2 nuclear translocation in the lung was examined by Western blotting. We found that melatonin administration significantly attenuated hepatic I/R induced lung injury in rats. Melatonin inhibited the pro-inflammatory responses and enhanced antioxidative responses. Melatonin alleviated pathological changes of the lung and liver, and inhibited apoptosis of cells in the lung. Phosphorylation of JNK, p38 and NF-ƙB and Nrf2 nuclear translocation was increased significantly in the lung by hepatic I/R. Melatonin administration inhibited the activation of JNK, p38, and NF-ƙB, however, melatonin further enhanced Nrf2 activation. We conclude that melatonin exerts a protective effect in hepatic I/R induced lung injury by attenuating the pro-inflammatory responses, inhibiting cell apoptosis, which was mediated in part through JNK, p38 MAPK, NF-ƙB and Nrf2 signaling pathways. Melatonin may be a promising therapeutic strategy for hepatic I/R induced lung injury.
Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Chengdu, 610041,China.
Li
L
Zhou
Department of Anesthesiology, Peking University People's Hospital, Peking, 100044, China.
Dong
D
Zhao
Department of Anesthesiology, Peking University People's Hospital, Peking, 100044, China.
Haiyan
H
An
Department of Anesthesiology, Peking University People's Hospital, Peking, 100044, China.
Hong
H
Zhang
Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Chengdu, 610041,China. Electronic address: jiang_chunling@yahoo.com.
Chunling
C
Jiang
Department of Anesthesiology, Peking University People's Hospital, Peking, 100044, China.
Baxian
B
Yang
D055371:Acute Lung Injury / Q000209:etiology* / Q000517:prevention & control*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D016207:Cytokines / Q000378:metabolism; D006499:Hepatic Artery / Q000473:pathology; D007511:Ischemia / Q000188:drug therapy; D008099:Liver / Q000098:blood supply*; D008297:Male; D008550:Melatonin / Q000627:therapeutic use*; D016328:NF-kappa B / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011169:Portal Vein / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications*; D015398:Signal Transduction / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D016207:Cytokines; D016328:NF-kappa B; D008550:Melatonin
Acute lung injury; Hepatic ischemia/reperfusion; MAPK signaling; Melatonin; NF-ƙB signaling; Nrf2 signaling