BACKGROUND: Acute liver failure(ALF) is a severe and lifethreatening clinical syndrome resulting in a high mortality and extremely poor prognosis. Recently, a water-soluble CO-releasing molecule(CORM-3) has been shown to have anti-inflammatory 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-Gal N in mice which were treated with CORM-3 or inactive CORM-3(i CORM-3). The efficacy of CORM-3 was evaluated based on survival, liver histopathology, serum aminotransferase activities(ALT and AST) and total bilirubin(TBi L). Serum levels of inflammatory cytokines(TNF-α, IL-6, IL-1β and IL-10) and liver immunohistochemistry of NF-κB-p65 were determined; the expression of inflammatory mediators such as i NOS, 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 TBi L. Furthermore, CORM-3 significantly inhibited the increased concentration of pro-inflammatory cytokines(TNF-α, IL-6 and IL-1β) and increased the anti-inflammatory cytokine(IL-10) productions in ALF mice. Moreover, CORM-3 significantly reduced the increased expression of i NOS and TLR4 in liver tissues and inhibited the nuclear expression of NF-κB-p65. CORM-3 had no effect on the increased expression of COX-2 in the ALF mice. An i CORM-3 failed to prevent acute liver damage induced by LPS/D-Gal N. CONCLUSION: These findings provided evidence that CORM-3 may offer a novel alternative approach for the management of ALF through anti-inflammatory functions. BACKGROUND: Acute liver failure (ALF) is a severe and lifethreatening clinical syndrome resulting in a high mortality and extremely poor prognosis. Recently, a water-soluble CO-releasing molecule (CORM-3) has been shown to have anti-inflammatory 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-Gal N in mice which were treated with CORM-3 or inactive CORM-3 ( i CORM-3). The efficacy of CORM-3 was evaluated based on survival, liver histopathology, serum aminotransferase activities (ALT and AST) and total bilirubin (TBi L). Serum levels of inflammatory cytokines , IL-1β and IL-10) and liver immunohistochemistry of NF-κB-p65 were determined; the expression of inflammatory mediators such as i NOS, 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 CORM-3 also decreased the levels of ALT, AST and TBi L. Furthermore, CORM-3 significantly inhibited the increased concentration of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β) and increased the anti CORM-3 had reduced the increased expression of iNOS and TLR4 in liver tissues and inhibited the nuclear expression of NF-κB-p65. CORM-3 had no effect on the increased expression of COX-2 in the ALF mice. An i CORM-3 failed to prevent acute liver damage induced by LPS / D-Gal N. CONCLUSION: These findings provided evidence that CORM-3 may offer a novel alternative approach for the management of ALF through anti-inflammatory functions.