The therapeutic effect of CORM-3 on acute liver failure induced by lipopolysaccharide/D-galactosamine in mice
| Autor: | Bing-Rong Liu, An-Chao Zhu, Yan-Fen Zhang, Hui Li, Bao-Shan Yang, Feng-Hua Pei, Xiao-Ren Wang, Bing-Zhu Yan |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Lipopolysaccharides
Male 0301 basic medicine Lipopolysaccharide Bilirubin medicine.medical_treatment Anti-Inflammatory Agents Galactosamine Inflammation Pharmacology Proinflammatory cytokine 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Organometallic Compounds Animals Medicine Aspartate Aminotransferases Hepatology business.industry Transcription Factor RelA Gastroenterology Alanine Transaminase Liver Failure Acute Mice Inbred C57BL Disease Models Animal 030104 developmental biology Cytokine Liver chemistry Cytoprotection 030220 oncology & carcinogenesis Immunology TLR4 Cytokines Chemical and Drug Induced Liver Injury Inflammation Mediators medicine.symptom business Biomarkers TBIL |
| Zdroj: | Hepatobiliary & Pancreatic Diseases International. 15:73-80 |
| ISSN: | 1499-3872 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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