title: Low dose of carbon monoxide intraperitoneal injection provides potent protection against GalN/LPS-induced acute liver injury in mice.
abstract: Carbon monoxide (CO) is an important effector-signaling molecule involved in various pathophysiological processes. Here we investigated the protective effects of exogenous CO in a murine model of acute liver damage induced by d-galactosamine (GalN) and lipopolysaccharide (LPS). Exogenous CO gas was administered to mice via intraperitoneal injection (first at a dose of 15 ml kg(-1) and then, 6 h later, 8 ml kg(-1)), which caused a significant elevation of blood carboxyhemoglobin levels of up to 12-14% for more than 12 h. GalN/LPS were given to induce acute liver damage in mice 30 min prior to CO exposure. This showed that GalN/LPS induced severe liver injury in mice, whereas CO injection remarkably improved the survival rate of mice and led to attenuated hepatocellular damage. CO exhibited anti-oxidative capabilities by inhibiting hepatic malondialdehyde contents and restoring superoxide dismutase and glutathione, as well as by reducing inducible NOS/NO production. The anti-apoptotic and anti-inflammatory effects of CO were substantial, characterized by a notable inhibition of hepatocyte apoptosis and a reduction of pro-inflammatory cytokines in mice. Our findings thus supported the hypothesis that exogenous CO provides protective effects against acute liver damage in mice, mainly dependent on its anti-oxidative, anti-inflammatory and anti-apoptotic properties.
authors.affiliation: Department of Anesthesiology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, People's Republic of China; Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, People's Republic of China.
authors.forename: Zongmei
authors.initials: Z
authors.lastname: Wen
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Tao
authors.initials: T
authors.lastname: Wen
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002248:Carbon Monoxide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002263:Carboxyhemoglobin / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005688:Galactosamine / Q000633:toxicity*; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D000975:Antioxidants; D016207:Cytokines; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D005688:Galactosamine; D002248:Carbon Monoxide; D002263:Carboxyhemoglobin