title: CO liberated from CORM-2 modulates the inflammatory response in the liver of thermally injured mice.
abstract: OBJECTIVE
  To explore the effects of CO-releasing molecules [tricarbonyldichlororuthenium (II) dimer, CORM-2]-liberated CO on attenuation of inflammatory responses in liver of an experimental animal model of thermal injury and to investigate the associated potential mechanisms.
  
  
  METHODS
  Thirty-six mice were assigned to three groups in three respective experiments. In each experiment, mice in sham group (n=4) received sham thermal injury, whereas mice in burn group (n=4) received a 15% of total body surface area (TBSA) full-thickness thermal injury, and mice in burn+CORM-2 group (n=4) received the same thermal injury with immediate administration of CORM-2 (8 mg/kg, iv). Hepatic tissue sections were stained with hematoxylin and eosin and examined under a light microscope. Levels of aminotransferases (ALT and AST) and nitric oxide (NO) were measured by biochemical methods. Tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL-1beta) activity, and the protein expression of iNOS and HO-1 in serum and tissue homogenates were assessed. In in vitro experiments, Kupffer cells were stimulated with LPS (10 microg/mL) for 4 h in the presence or absence of CORM-2 (10-100 micromol/L). Subsequently, the expression levels of TNF-alpha and NO production were assessed.
  
  
  RESULTS
  Pro-inflammatory mediators (TNF-alpha, IL-1beta, NO) in serum and liver homogenates of thermally injured mice were significantly reduced by CORM-2 administration. This was accompanied by a decrease in the expression of iNOS while an increase in the expression of HO-1 in the liver tissue. In parallel, the concentrations of TNF-alpha and NO in supernatants of LPS-stimulated Kupffer cells co-incubated with CORM-2 (10-100 micromol/L) were also markedly decreased. Histological examination demonstrated that CORM-2 could attenuate the leukocytes infiltration to the liver tissue.
  
  
  CONCLUSIONS
  CORM-released CO modulates liver inflammation and significantly protects liver injury in burn mice by inhibiting the expression of iNOS and NO production, down-regulating the expression of pro-inflammatory mediators (TNF-alpha, IL-1beta).
authors.affiliation: Department of Burns and Plastic Surgery, Affiliated Hospital, Jiangsu University, 438 Jiefang Rd. Zhenjiang 212001, Jiangsu Province, China. sunbinwe@hotmail.com
authors.forename: Bing-Wei
authors.initials: BW
authors.lastname: Sun
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Sun
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D002056:Burns / Q000150:complications* / Q000276:immunology; D002248:Carbon Monoxide / Q000378:metabolism*; D006505:Hepatitis / Q000188:drug therapy* / Q000209:etiology; D018836:Inflammation Mediators / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009942:Organometallic Compounds / Q000493:pharmacokinetics*
chemical_list: D018836:Inflammation Mediators; D009942:Organometallic Compounds; C447082:tricarbonyldichlororuthenium (II) dimer; D002248:Carbon Monoxide