Effects of nitric oxide syntase-inhibitors on early hepatic fibrosis induced by bile duct ligation

2002 ◽  
Vol 36 ◽  
pp. 50
Author(s):  
M.Jose Mesonero ◽  
M.Jose Vazquez-Gil ◽  
Olga Flores ◽  
Manuela Criado ◽  
Jose M. Lopez-Novoa ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Bile Duct ◽  
Hepatic Fibrosis ◽  
Bile Duct Ligation ◽  
Duct Ligation

Effects of chronic nitric oxide activation or inhibition on early hepatic fibrosis in rats with bile duct ligation

1999 ◽  
Vol 96 (3) ◽  
pp. 297-305 ◽  
Author(s):  
Paula MAYORAL ◽  
Manuela CRIADO ◽  
Froilan HIDALGO ◽  
Olga FLORES ◽  
Miguel A. ARÉVALO ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Bile Duct ◽  
Nitric Oxide Synthase ◽  
Hepatic Fibrosis ◽  
Bile Duct Ligation ◽  
Common Bile Duct Ligation ◽  
Western Blots ◽  
Circulatory Effects ◽  
Duct Ligation ◽  
Oxide Synthase

Hepatic fibrosis or increased liver collagen contents drive functional abnormalities that, when extensive, may be life threatening. The purpose of this study was to assess the effects of the chronic stimulation or inhibition of nitric oxide synthesis in rats with hepatic fibrosis induced by permanent common bile duct ligation (3 weeks) and the role of expression of the different nitric oxide synthase isoforms. Bile duct ligation led to an important accumulation of collagen in the hepatic parenchyma, as shown both histologically and by the hydroxyproline contents of livers. Bilirubin and serum enzyme activities (measured as markers of cholestasis) increased several-fold after bile duct ligation. The area of fibrotic tissue, liver hydroxyproline content and serum markers of cholestasis were clearly related in obstructed rats. The absence of modifications in haemodynamic parameters excludes circulatory changes from being responsible for the development of liver alterations. In animals treated with NG-nitro-L-arginine methyl ester (L-NAME) the area of fibrosis was similar to that of untreated animals, the signs of cholestasis and cellular injury being more evident. In rats treated with L-arginine the area of fibrosis was almost three times larger than that found in bile duct ligated rats and in L-NAME-treated bile duct ligated rats, although the observed biochemical changes were similar to those seen in rats treated with L-NAME. Our results with inducible nitric oxide synthase, obtained by Western blots and immunohistochemistry, indicate a greater expression of the inducible enzyme in bile duct ligated and L-arginine-treated animals and a lower expression in the L-NAME and control groups. Constitutive nitric oxide synthase expression, obtained by Western blots, was very similar in all groups, except for the L-arginine-treated rats in which it was lower. These results suggest that nitric oxide production may be a key factor in the development of fibrosis in bile duct ligated rats. They also support the hypothesis of a dual role for nitric oxide; one beneficial, mediated by its circulatory effects, and the second negative, through its local toxic effects.

Effects of chronic nitric oxide activation or inhibition on early hepatic fibrosis in rats with bile duct ligation

1999 ◽  
Vol 96 (3) ◽  
pp. 297 ◽  
Author(s):  
Paula MAYORAL ◽  
Manuela CRIADO ◽  
Froilan HIDALGO ◽  
Olga FLORES ◽  
Miguel A. ARÉVALO ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Bile Duct ◽  
Hepatic Fibrosis ◽  
Bile Duct Ligation ◽  
Duct Ligation

Regulation of inducible nitric oxide synthase and nitric oxide during hepatic injury and fibrogenesis

1997 ◽  
Vol 273 (1) ◽  
pp. G124-G130 ◽  
Author(s):  
D. C. Rockey ◽  
J. J. Chung
Keyword(s):  
Nitric Oxide ◽  
Carbon Tetrachloride ◽  
Bile Duct ◽  
Kupffer Cells ◽  
Hepatic Injury ◽  
Bile Duct Ligation ◽  
Inos Mrna ◽  
No Production ◽  
Nonparenchymal Cells ◽  
Duct Ligation

Nitric oxide (NO) production via inducible NO synthase (iNOS) is prominent in the liver after stimulation with cytokines and/or lipopolysaccharide. The aim of this study was to investigate the production of NO via iNOS in specific liver cell populations during toxin-mediated and obstructive hepatic injury and fibrogenesis. After a single dose of carbon tetrachloride, iNOS mRNA and nitrite (a metabolic product of NO) were detected only in Kupffer cells. They were not detectable in any cell type after recurrent administration of carbon tetrachloride, including in animals with far advanced cirrhosis (i.e., portal hypertension and/or ascites). After bile duct ligation, a mechanistically different form of liver injury and fibrogenesis, iNOS mRNA and nitrite were identified in all nonparenchymal cells but not in hepatocytes. Twenty-four hours after bile duct ligation, iNOS mRNA and NO production were greatest in Kupffer cells, but after prolonged bile duct ligation, iNOS was found predominantly in sinusoidal endothelial cells. These data indicate that iNOS expression varies temporally and spatially in the liver after injury and also varies with the type of insult.

scholarly journals Preventive effects of ME3738 on hepatic fibrosis induced by bile duct ligation in rats

2008 ◽  
Vol 38 (7) ◽  
pp. 727-735 ◽  
Author(s):  
Kazunori Maeda ◽  
Masahiko Koda ◽  
Tomomitsu Matono ◽  
Takaaki Sugihara ◽  
Satoru Yamamoto ◽  
...  
Keyword(s):  
Bile Duct ◽  
Hepatic Fibrosis ◽  
Bile Duct Ligation ◽  
Duct Ligation ◽  
Preventive Effects

495 Intrapulmonary vascular dilatation and nitric oxide in hypoxemic rats with chronic bile duct ligation

Hepatology ◽  
2003 ◽  
Vol 38 ◽  
pp. 398-398
Author(s):  
X ZHANG ◽  
Y KATSUTA ◽  
T AKIMOTO ◽  
M OHSUGA ◽  
Y KATO ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Bile Duct ◽  
Bile Duct Ligation ◽  
Duct Ligation ◽  
Vascular Dilatation

[335] THE ANTI-FIBROTIC EFFECTS OF CELECOXIB IN BILE DUCT LIGATION- AND THIOACETAMIDE-INDUCED HEPATIC FIBROSIS MODELS IN RAT

2007 ◽  
Vol 46 ◽  
pp. S131
Author(s):  
Y.H. Paik ◽  
S.H. Kang ◽  
H.J. Lee ◽  
S.H. Ahn ◽  
K.H. Han ◽  
...  
Keyword(s):  
Bile Duct ◽  
Hepatic Fibrosis ◽  
Bile Duct Ligation ◽  
Duct Ligation

M1567 CpG Motifs Induce Proinflammatory Events in Hepatic Stellate Cells and Are Involved in Bile Duct Ligation-Induced Hepatic Fibrosis In Vivo

2008 ◽  
Vol 134 (4) ◽  
pp. A-795
Author(s):  
Erwin Gäbele ◽  
Matthias Froh ◽  
Reiner Wiest ◽  
Florian Obermeier ◽  
Jürgen Schölmerich ◽  
...  
Keyword(s):  
Bile Duct ◽  
Hepatic Fibrosis ◽  
Hepatic Stellate Cells ◽  
Bile Duct Ligation ◽  
Stellate Cells ◽  
Cpg Motifs ◽  
Duct Ligation
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