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| The therapeutic effect of CORM-3 on acute liver failure induced by lipopolysaccharide/D-galactosamine in mice |
| Bing-Zhu Yan, Bao-Shan Yang, Hui Li, Yan-Fen Zhang, Feng-Hua Pei, An-Chao Zhu, Xiao-Ren Wang and Bing-Rong Liu |
Harbin, China
Author Affiliations: Department of Infectious Diseases (Yan BZ, Yang BS and Wang XR), Department of Gastroenterology and Hepatology (Li H, Pei FH and Liu BR) and Department of Laboratory Diagnosis (Zhang YF), The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China; Department of Histology, The First Hospital of Harbin City, Harbin 150001, China (Zhu AC)
Corresponding Author: Bing-Rong Liu, MD, Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China (Tel/Fax: +86-451-86605980; Email: bingrongliu@qq.com) |
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Abstract 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-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-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 activities (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-κB-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-inflammatory cytokine (IL-10) productions in ALF mice. Moreover, CORM-3 significantly 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 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.
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2016, Vol. 15 
