Involvement of reactive oxygen species and nitric oxide radicals in activation and proliferation of rat hepatic stellate cells

G Svegliati-Baroni*, S Saccomanno, H van Goor, P Jansen, A Benedetti, H Moshage

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

129 Citations (Scopus)

Abstract

Background/Aims: Reactive oxygen species (ROS) induce HSCs activation, proliferation and collagen gene expression in vitro. Nitric oxide (NO) represents a reactive molecule that reacts with ROS, yielding peroxynitrite. We thus verified the effect of NO on ROS-induced HSCs proliferation in vitro and correlated iNOS expression and ROS formation to HSCs activation in the early phase of liver injury leading to hepatic fibrosis in vivo. Methods/Results: HSCs were incubated with iron ascorbate (FeAsc) in vitro, which induced ROS production, ERK1/2 phosphorylation and increased cell proliferation. This effect was significantly reduced by the presence of the NO donor S-nitroso-N-acetylpenicillamine. Liver injury was induced in vivo in rats by dimethylnitrosamine administration. HSCs activation started 6 h after DMN administration and peaked at 1 week. ROS generation and neutrophil infiltration were evident for at least 48 h after DMN treatment, showing an identical distribution pattern. Only a few inflammatory cells expressed iNOS 6 h after DMN administration. Conclusions: we have shown that NO acts as a ROS scavenger in vitro, thus inhibiting HSCs proliferation. ROS production by infiltrating neutrophils occurs in the early phase of liver fibrosis and can represent a stimulus to HSCs activation in vivo. The reduced iNOS expression may account for the low NO levels and the inability to prevent the ROS-induced HSC activation in vivo.

Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalLiver
Volume21
Issue number1
Publication statusPublished - Feb-2001
Event33rd Annual Meeting of the European-Association-for-the-Study-of-the-Liver - , Portugal
Duration: 15-Apr-199818-Apr-1998

Keywords

  • liver injury
  • reactive oxygen species
  • nitric oxide
  • hepatic stellate cells
  • SYNTHASE GENE-TRANSFER
  • FAT-STORING CELLS
  • OXIDATIVE STRESS
  • LIPID-PEROXIDATION
  • LIVER-DAMAGE
  • PHOSPHATIDYLINOSITOL 3-KINASE
  • MONOCLONAL-ANTIBODY
  • SIGNAL-TRANSDUCTION
  • INHIBITION
  • SUPEROXIDE

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