CO liberated from CORM-2 modulates the inflammatory response in the liver of thermally injured mice.

Abstract

AIM:

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.

CONCLUSION:

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: Bing-Wei Sun, Yan Sun, Zhi-Wei Sun, Xi Chen
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 14 Issue 4 Pg. 547-53 (Jan 28 2008) ISSN: 1007-9327 [Print] United States
• PMID: 18203286 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Inflammation Mediators
• Organometallic Compounds
• tricarbonyldichlororuthenium (II) dimer
• Carbon Monoxide

Topics

• Animals
• Burns (complications, immunology)
• Carbon Monoxide (metabolism)
• Hepatitis (drug therapy, etiology)
• Inflammation Mediators (metabolism)
• Liver (drug effects, immunology)
• Male
• Mice
• Mice, Inbred C57BL
• Organometallic Compounds (pharmacokinetics)