Antifibrotic and hemodynamic effects of the early and chronic administration of octreotide in two models of liver fibrosis in rats.
The aim of this study was to assess the effect of the early and chronic administration of octreotide in the prevention of hepatic fibrosis and portal hypertension (PHT). Two experimental models of liver fibrosis caused by bile duct ligation (BDL) or CCl4 were divided into 4 rat groups: sham, placebo, and octreotide (10 and 100 micrograms/kg twice daily, subcutaneously). Liver fibrosis was assessed by the area of fibrosis (image analysis), liver hydroxyproline and fibronectin mRNA contents, and serum hyaluronate. Systemic and splanchnic hemodynamic changes were also evaluated, including the splenorenal shunt blood flow by the transit-time ultrasound (TTU) technique. In both models, splenorenal shunt blood flow was significantly lower in the octreotide groups than in the placebo group (P <.05), while portal pressure was not significantly decreased. There was a significant decrease in fibrosis by octreotide in the CCl4 model only: area of fibrosis: 13.9% +/- 3.7% vs. 9.8% +/- 2.5% (P <.01), hydroxyproline: 1.8 +/- 0.6 vs. 1.3 +/- 0.4 mg/g wet liver (P <.05), respectively, placebo vs. octreotide 10 micrograms/kg. There was a significant correlation between the area of fibrosis and hydroxyproline liver content (r =.87 in the biliary model and r =.91 in the CCl4 model; P <.0001). The early and chronic administration of octreotide prevents the development of portocollateral blood flow without reducing portal pressure in two models of liver fibrosis and the development of liver fibrosis in the CCl4 model.
Fort
J
J
Laboratoire d'Hémodynamique Splanchnique, Université d'Angers, Bordeaux, France.
Oberti
F
F
Pilette
C
C
Veal
N
N
Gallois
Y
Y
Douay
O
O
Rousselet
M C
MC
Rosenbaum
J
J
Calès
P
P
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D005353:Fibronectins / Q000235:genetics; D005355:Fibrosis / Q000517:prevention & control; D006439:Hemodynamics / Q000187:drug effects; D006820:Hyaluronic Acid / Q000097:blood; D006909:Hydroxyproline / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008102:Liver Circulation / Q000187:drug effects*; D008106:Liver Cirrhosis, Experimental / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D015282:Octreotide / Q000008:administration & dosage* / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014662:Vasoconstrictor Agents / Q000008:administration & dosage* / Q000494:pharmacology
D005353:Fibronectins; D012333:RNA, Messenger; D014662:Vasoconstrictor Agents; D006820:Hyaluronic Acid; D006909:Hydroxyproline; D015282:Octreotide