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Carbon monoxide (CO)‐releasing molecule (CORM)‐liberated CO attenuates inflammatory response in the liver of thermally‐injured mice
Author(s) -
Sun BingWei,
Bihari Aurelia,
Chen Xi,
Chen ZhaoYong,
Tai Ningzheng,
Potter Richard F,
Cepinskas Gediminas
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a768-b
Subject(s) - liver injury , chemistry , tumor necrosis factor alpha , inflammation , medicine , western blot , pharmacology , endocrinology , immunology , biochemistry , gene
CORMs are emerging as potent regulators of inflammatory response. In this study, we assessed the effects and potential mechanisms of CORM‐2‐liberated CO on inflammatory response in the liver of burn (dorsal skin full‐thickness thermal injury; 15% total body surface area–TBSA)‐challenged mice. CORM‐2 (8mg/kg; i.v.) was administrated immediately after burn induction. Serum levels of alanine aminotransferase (ALT), TNF‐α, IL‐1β (ELISA), and tissue expression of HO‐1, iNOS and ICAM‐1 (Western blots), along with activation of NFκB (EMSA) and accumulation of PMN (MPO assay) in the liver were assessed 24 hrs following burn induction. The obtained results indicate that induction of 15% TBSA dorsal skin thermal injury in mice results in an increase in circulating levels of ALT (a marker of liver injury) and pro‐inflammatory cytokines, TNF‐α and IL‐1β. This was accompanied by activation of NFκB, increased expression of ICAM‐1 and subsequent PMN accumulation in the liver of burn‐challenged mice. In parallel, HO‐1 and iNOS protein expression in the liver were also up‐regulated. The above changes were significantly attenuated in CORM‐2‐treated mice, except for the expression of HO‐1 which was further amplified in the liver of burn‐challenged mice treated with CORM‐2. These findings indicate that CO released by systemically administered CORM‐2 provides liver with the anti‐inflammatory stimulus and improves liver function in burn‐injured mice (HSFO‐NA5580, MOP‐68848 and NNSF China‐39970862)