Early colchicine administration reduces hepatic fibrosis and portal hypertension in rats with bile duct ligation.
Chronic administration of colchicine has been suggested as a potential treatment for hepatic fibrosis. The purpose of this study was to examine the effects of chronic oral administration of colchicine on the histological and hemodynamic abnormalities of bile duct ligation in the rat. Forty-eight rats with ligation-section of the common bile duct were randomly and blindly assigned to receive either colchicine (50 mu/kg day) or placebo by gavage for 4 weeks. At the end of the treatment period, morphometric analysis showed that hepatocyte and sinusoidal volume fractions were significantly higher in rats treated with colchicine than in rats receiving placebo (42.4 +/- 1.3 vs. 32.1 +/- 2.6% (mean +/- S.E.) and 8.3 +/- 0.6 vs 4.7 +/- 0.4%, respectively), while bile duct volume fractions (reflecting bile ductular proliferation) and connective tissue fractions were significantly lower in rats treated with colchicine than in rats receiving placebo (12.1 +/- 0.9 vs. 17.0 +/- 0.1% and 37.2 +/- 0.9 vs. 46.1 +/- 2.0%, respectively). Portal pressure (13.4 +/- 0.7 vs. 17.8 +/- 0.5 mmHg), portal tributary blood flow (5.8 +/- 0.4 vs. 8.7 +/- 0.5 ml.min-1.100 g-1) and cardiac index (40.8 +/- 2.3 vs. 50.6 +/- 1.5 ml.min-1.100 g-1) were significantly lower in colchicine-treated rats than in placebo treated animals. In conclusion, in rats with bile duct ligation, colchicine limits the severity of liver lesions and, consequently, of portal hypertension and hyperkinetic syndrome.
Poo
J L
JL
Laboratoire d'Hemodynamique Splanchnique, Unité de Recherches de Physiopathologie Hépatique (INSERM U-24), Hôpital Beaujon, Clichy, France.
Feldmann
G
G
Moreau
A
A
Gaudin
C
C
Lebrec
D
D
D000284:Administration, Oral; D000818:Animals; D001652:Bile Ducts; D003078:Colchicine / Q000008:administration & dosage*; D004311:Double-Blind Method; D004353:Drug Evaluation, Preclinical; D006975:Hypertension, Portal / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008026:Ligation; D008099:Liver / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013152:Splanchnic Circulation / Q000502:physiology; D013997:Time Factors
D003078:Colchicine