Influences of reactive oxygen species and nitric oxide on hepatic fibrogenesis

Gennadiy Novitskiy, James J. Potter, Lan Wang, Esteban Mezey

Research output: Contribution to journalArticlepeer-review

Abstract

Background/Aims: This study determined the roles of NAD(P)H oxidase, which generates reactive oxygen species (ROS), and of inducible nitric oxide synthase (iNOS), which generates nitric oxide (NO) on the development of hepatic fibrosis in mice. Methods: Hepatic fibrosis was produced by carbon tetrachloride administered for 12 weeks in wild-type (WT) mice and in mice with knockout of either the gp91phox subunit of the NAD(P)H complex (gp91phox-/-) or of iNOS (iNOS-/-). Results: Liver fibrosis and hydroxyproline after carbon tetrachloride was lower in gp91phox-/- and in iNOS-/- mice than in WT mice. The increase in α2(I) collagen mRNA was absent in the gp91phox-/- but not in the iNOS-/- mice. Transformation growth factor β (TGF-β) mRNA was increased more in the gp91phox-/- than in the WT mice, while in the iNOS-/- mice there was no increase in TGF-β mRNA. 3-Nitrotyrosine was similarly increased by carbon tetrachloride in gp91phox-/- and WT mice, while there was no increase in the iNOS-/- mice. Conclusions: Deficiencies in NAD(P)H oxidase and in iNOS separately reduce, but do not eliminate carbon tetrachloride-induced liver fibrosis. Likely causes for this inhibitory effects are decreases in the production of ROS in NAD(P)H deficiency and of peroxinitrite radicals in iNOS deficiency.

Original languageEnglish (US)
Pages (from-to)1248-1257
Number of pages10
JournalLiver International
Volume26
Issue number10
DOIs
StatePublished - Dec 2006

Keywords

  • Liver fibrosis
  • Nitric oxide
  • Reactive oxygen species

ASJC Scopus subject areas

  • Hepatology

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