title: Methane Attenuates Hepatic Ischemia/Reperfusion Injury in Rats Through Antiapoptotic, Anti-Inflammatory, and Antioxidative Actions.
abstract: Hepatic ischemia/reperfusion (I/R) injury, which occurs in various diseases, introduces severe tissue damage and liver dysfunction. However, no promising therapies for such a significant condition currently exist. Methane has been suggested to exert a protective effect against intestinal I/R injury. In this study, we introduced methane to treat hepatic I/R injury to show its promising protective effect. Also, intraperitoneal injection with methane-rich saline, which could have potential clinical applications, was applied as a new method. Partial liver warm ischemia was applied in Sprague-Dawley rats for 60 min followed by succedent reperfusion. In the test for effective dosage, methane-rich saline was administrated intraperitoneally to the rats at doses of 1, 5, 20, or 40 mL/kg at onset of reperfusion. In the test for protective effect, rats received methane-rich saline intraperitoneally at a dose of 10 mL/kg before the initiation of reperfusion. We found that methane-rich saline significantly decreased serum alanine aminotransferase, aspartate aminotransferase activity, and the occurrence of necrosis. Moreover, methane-rich saline reduced the amount of caspase-3 and the number of apoptotic cells. In addition, methane-rich saline increased the level of superoxide dismutase and decreased the level of malondialdehyde and 8-hydroxyguanosine. Furthermore, research indicated that methane-rich saline markedly decreased gene expression and content of tumor necrosis factor-α and interleukin-6. Also, reduced CD68-positive cells showed decreased inflammatory cells in the liver. Our results suggest that methane protects the liver against I/R injury through antiapoptotic, antioxidative, and anti-inflammatory actions.
authors.affiliation: *Department of Navy Aeromedicine, Second Military Medical University; and †Graduate Management Unit, Second Military Medical University, Shanghai, China; ‡Department of Emergency, Disaster and Critical Care Medicine, Hyogo College of Medicine, Nishinomiya, Japan; and §Department of Nautical Medicine, Nantong University, Jiangsu, China.
authors.forename: Zhouheng
authors.initials: Z
authors.lastname: Ye
authors.forename: Ouyang
authors.initials: O
authors.lastname: Chen
authors.forename: Rongjia
authors.initials: R
authors.lastname: Zhang
authors.forename: Atsunori
authors.initials: A
authors.lastname: Nakao
authors.forename: Danfeng
authors.initials: D
authors.lastname: Fan
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.forename: Zhengyong
authors.initials: Z
authors.lastname: Gu
authors.forename: Hengyi
authors.initials: H
authors.lastname: Tao
authors.forename: Xuejun
authors.initials: X
authors.lastname: Sun
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry*; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D000975:Antioxidants / Q000737:chemistry*; D017209:Apoptosis; D001219:Aspartate Aminotransferases / Q000097:blood; D053148:Caspase 3 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006151:Guanosine / Q000031:analogs & derivatives / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008697:Methane / Q000008:administration & dosage / Q000737:chemistry*; D009336:Necrosis / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy*; D013482:Superoxide Dismutase / Q000378:metabolism; D052096:Warm Ischemia; D000097382:CD68 Molecule
chemical_list: D000410:Alanine Transaminase; D000893:Anti-Inflammatory Agents; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000975:Antioxidants; D001219:Aspartate Aminotransferases; D053148:Caspase 3; D006151:Guanosine; D008315:Malondialdehyde; D008697:Methane; D013482:Superoxide Dismutase; C539355:CD68 protein, rat; D000097382:CD68 Molecule; C046215:8-hydroxyguanosine