| 17105591 |
Novitskiy G, Potter JJ, Wang L, Mezey E: Influences of reactive oxygen species and nitric oxide on hepatic fibrogenesis. Liver Int. 2006 Dec;26(10):1248-57.
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 alpha2 (I) collagen mRNA was absent in the gp91phox-/- but not in the iNOS (-/-) mice. Transformation growth factor beta (TGF-beta) mRNA was increased more in the gp91phox-/- than in the WT mice, while in the iNOS (-/-) mice there was no increase in TGF-beta 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. |
87(1,1,2,2) |