BACKGROUND: Acute liver failure (ALF) is a severe and life- threatening clinical syndrome resulting in a high mortality and extremely poor prognosis. Recently, a water-soluble CO-releas- ing molecule (CORM-3) has...BACKGROUND: Acute liver failure (ALF) is a severe and life- threatening clinical syndrome resulting in a high mortality and extremely poor prognosis. Recently, a water-soluble CO-releas- ing molecule (CORM-3) has been shown to have anti-inflam- matory effect. The present study was to investigate the effect of CORM-3 on ALF and elucidate its underlying mechanism. METHODS: ALF was induced by a combination of LPS/D-GalN in mice which were treated with CORM-3 or inactive CORM-3 (iCORM-3). The efficacy of CORM-3 was evaluated based on survival, liver histopathology, serum aminotransferase activi- ties (ALT and AST) and total bilirubin (TBiL). Serum levels of inflammatory cytokines (TNF-α, IL-6, IL-1β and IL-10) and liver immunohistochemistry of NF-KB-p65 were determined; the expression of inflammatory mediators such as iNOS, COX-2 and TLR4 was measured using Western blotting. RESULTS: The pretreatment with CORM-3 significantly improved the liver histology and the survival rate of mice compared with the controls; CORM-3 also decreased the levels of ALT, AST and TBiL. Furthermore, CORM-3 significantly inhibited the increased concentration of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β) and increased the anti-in- flammatory cytokine (IL-10) productions in ALF mice. More- over, CORM-3 significantly reduced the increased expression of iNOS and TLR4 in liver tissues and inhibited the nudear ex- pression of NF-KB-p65. CORM-3 had no effect on the increased expression of COX-2 in the ALF mice. An iCORM-3 failed to prevent acute liver damage induced by LPS/D-GalN. CONCLUSION: These findings provided evidence that CORM-3 may offer a novel alternative approach for the management of ALF through anti-inflammatory functions.展开更多
基金supported by a grant from the Science and Technology Research Foundation of Educational Committee,Heilongjiang Province,China(12531294)
文摘BACKGROUND: Acute liver failure (ALF) is a severe and life- threatening clinical syndrome resulting in a high mortality and extremely poor prognosis. Recently, a water-soluble CO-releas- ing molecule (CORM-3) has been shown to have anti-inflam- matory effect. The present study was to investigate the effect of CORM-3 on ALF and elucidate its underlying mechanism. METHODS: ALF was induced by a combination of LPS/D-GalN in mice which were treated with CORM-3 or inactive CORM-3 (iCORM-3). The efficacy of CORM-3 was evaluated based on survival, liver histopathology, serum aminotransferase activi- ties (ALT and AST) and total bilirubin (TBiL). Serum levels of inflammatory cytokines (TNF-α, IL-6, IL-1β and IL-10) and liver immunohistochemistry of NF-KB-p65 were determined; the expression of inflammatory mediators such as iNOS, COX-2 and TLR4 was measured using Western blotting. RESULTS: The pretreatment with CORM-3 significantly improved the liver histology and the survival rate of mice compared with the controls; CORM-3 also decreased the levels of ALT, AST and TBiL. Furthermore, CORM-3 significantly inhibited the increased concentration of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β) and increased the anti-in- flammatory cytokine (IL-10) productions in ALF mice. More- over, CORM-3 significantly reduced the increased expression of iNOS and TLR4 in liver tissues and inhibited the nudear ex- pression of NF-KB-p65. CORM-3 had no effect on the increased expression of COX-2 in the ALF mice. An iCORM-3 failed to prevent acute liver damage induced by LPS/D-GalN. CONCLUSION: These findings provided evidence that CORM-3 may offer a novel alternative approach for the management of ALF through anti-inflammatory functions.