Targeted delivery of ribavirin improves outcome of murine viral fulminant hepatitis via enhanced anti-viral activity
| Autor: | Pieter Biessels, David S. Bell, M. James Phillips, Nancy Ng, Laisum Fung, Ian D. McGilvray, Gord Adamson, Caroline Woods, Reginald M. Gorczynski, Louise A. Scrocchi, Max Ma, Adam Levy, Cheryl Koscik, William He, Steve Brookes, Andrea Rowe, Gary A. Levy, Anand Ghanekar |
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| Rok vydání: | 2006 |
| Předmět: |
Hepatitis C virus
viruses Viral Hepatitis medicine.disease_cause Virus Replication Antiviral Agents Proinflammatory cytokine chemistry.chemical_compound Mice Drug Delivery Systems Outcome Assessment Health Care Ribavirin medicine Animals Fulminant hepatitis Hepatitis Mice Inbred BALB C Murine hepatitis virus Hepatology business.industry Macrophages virus diseases Liver Failure Acute medicine.disease chemistry Hepatitis Viral Animal Immunology Hepatocytes Tumor necrosis factor alpha Female Viral disease Viral hepatitis business Coronavirus Infections |
| Zdroj: | Hepatology (Baltimore, Md.) |
| ISSN: | 0270-9139 |
| Popis: | Side effects of interferon–ribavirin combination therapy limit the sustained viral response achievable in hepatitis C virus (HCV) patients. Coupling ribavirin to macromolecular carriers that target the drug to the liver would reduce systemic complications. The aim of this study was to evaluate the efficacy of a hemoglobin–ribavirin conjugate (HRC 203) in murine hepatitis virus strain 3 (MHV‐3) induced viral hepatitis. HRC 203 had greater anti‐viral activity on both isolated hepatocytes and macrophages, whereas both ribavirin and HRC 203 inhibited production of the pro‐inflammatory cytokines interferon gamma (IFN‐γ) and tumor necrosis factor alpha (TNF‐α) by macrophages. In vivo, untreated MHV‐3–infected mice all developed clinical and biochemical signs of acute viral hepatitis and died by day 4 post infection. Livers recovered from untreated infected mice showed greater than 90% necrosis. In contrast, survival was enhanced in both ribavirin‐ and HRC 203–treated mice with a marked reduction in biochemical [ALTmax 964 ± 128 IU/L (ribavirin); 848 ± 212 IU/L (HRC 203)] and histological evidence of hepatic necrosis ( |
| Databáze: | OpenAIRE |
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