Anti-hepatitis B virus activities of α-DDB-FNC, a novel nucleoside-biphenyldicarboxylate compound in cells and ducks, and its anti-immunological liver injury effect in mice

Antiviral Res. 2012 Dec;96(3):333-9. doi: 10.1016/j.antiviral.2012.10.003. Epub 2012 Oct 23.

Abstract

Infection with hepatitis B virus (HBV) continues to be a major global cause of acute and chronic liver disease with high mortality. Herein, we examined both the anti-HBV and hepatoprotective activity of α-DDB-FNC. In human HBV-transfected liver cell line HepG2.2.15, α-DDB-FNC effectively suppressed the secretion of HBV antigens in a time and dose-dependent manner with 25.11% inhibition on HBeAg and 43.68% on HBsAg at 2.5 μM on day 9. Consistent with the HBV antigen reduction, α-DDB-FNC (2.5 μM) also reduced HBV DNA level by 77.74% extracellularly and 78.94% intracellularly on day 9. In the duck hepatitis B virus (DHBV) infected ducks, after α-DDB-FNC was given once daily for 10 days, the serum and liver DHBV DNA levels were reduced markedly with 96.81% and 97.21% at 10 mgkg(-1) on day 10, respectively. In Con A-induced immunological liver-injury mice, α-DDB-FNC significantly inhibited the elevation of serum ALT, AST, TBiL and liver MDA, NO levels. Furthermore, significant improvement of the liver was observed after α-DDB-FNC treatment both in ducks and mice, as evaluated by the histopathological analysis. In conclusion, our results demonstrated that α-DDB-FNC possesses both antiviral activity against HBV and hepatoprotective effect to Con A-induced liver-injury mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology*
  • Benzodioxoles / pharmacology
  • Cell Survival / drug effects
  • Chemical and Drug Induced Liver Injury / drug therapy
  • Chemical and Drug Induced Liver Injury / pathology
  • Concanavalin A / toxicity
  • Cytidine / analogs & derivatives*
  • Cytidine / pharmacology
  • Cytoprotection
  • DNA Replication
  • DNA, Viral / analysis
  • Dose-Response Relationship, Drug
  • Ducks / virology*
  • Hep G2 Cells
  • Hepatitis B / drug therapy
  • Hepatitis B / virology
  • Hepatitis B Surface Antigens / metabolism
  • Hepatitis B e Antigens / metabolism
  • Hepatitis B virus / drug effects*
  • Hepatitis B virus / genetics
  • Hepatitis B virus / physiology
  • Humans
  • Liver / drug effects
  • Liver / virology
  • Male
  • Mice
  • Time Factors
  • Virus Replication / drug effects

Substances

  • 4'-azido-2'-deoxy-2'-fluoro-3'-(4,4'-dimethoxy-2'-methoxycarbonyl-5,6,5',6'-bis(methylenedioxy)-1,1'-biphenyl-2-carboxyl)cytidine
  • Antiviral Agents
  • Benzodioxoles
  • DNA, Viral
  • Hepatitis B Surface Antigens
  • Hepatitis B e Antigens
  • Concanavalin A
  • Cytidine