Liver international : official journal of the International Association for the Study of the Liver · 2004
Halofuginone can worsen liver fibrosis in bile duct obstructed rats.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Van de Casteele Marc, Roskams Tania, Van der Elst Ingrid, van Pelt Jos F, Fevery Johan, Nevens Frederik
Аннотация
BACKGROUND/AIMS: Halofuginone (HF) is an antifibrotic agent in rat models of liver fibrosis caused by repetitive intoxications. A beneficial effect of HF on a biliary type of liver fibrosis has not been proven yet.
METHODS: Bile duct-obstructed rats were given HF from the moment of obstruction onwards and compared with no treatment. After 3 weeks, respectively, 6 weeks, aminopyrine breath test (ABT) and haemodynamic measurements including of portal pressure were carried out. Liver pieces were taken for Sirius red quantitative scoring, as well as for semiquantitative determinations of collagen type I and III RNA levels.
RESULTS: ABT was significantly worse in HF-treated rats as compared with no treatment (P=0.02). Haemodynamic data and collagen type I and III determinations were not significantly different between groups. Biliary fibrosis scores were significantly higher in HF-treated rats as compared with no treatment (P=0.03). More Sirius red staining was associated with more proliferation of bile ductules.
CONCLUSIONS: HF may worsen biliary fibrosis. This contrasts sharply with antifibrotic effects in other models of liver fibrosis. Distinctive cellular mechanisms in biliary fibrosis may explain this discrepancy. One should be cautious for chronic application of HF in man with cholestasis.
METHODS: Bile duct-obstructed rats were given HF from the moment of obstruction onwards and compared with no treatment. After 3 weeks, respectively, 6 weeks, aminopyrine breath test (ABT) and haemodynamic measurements including of portal pressure were carried out. Liver pieces were taken for Sirius red quantitative scoring, as well as for semiquantitative determinations of collagen type I and III RNA levels.
RESULTS: ABT was significantly worse in HF-treated rats as compared with no treatment (P=0.02). Haemodynamic data and collagen type I and III determinations were not significantly different between groups. Biliary fibrosis scores were significantly higher in HF-treated rats as compared with no treatment (P=0.03). More Sirius red staining was associated with more proliferation of bile ductules.
CONCLUSIONS: HF may worsen biliary fibrosis. This contrasts sharply with antifibrotic effects in other models of liver fibrosis. Distinctive cellular mechanisms in biliary fibrosis may explain this discrepancy. One should be cautious for chronic application of HF in man with cholestasis.
Предметные рубрики MeSH
AminopyrineAnimalsBile DuctsBreath TestsCholestasis, ExtrahepaticCollagen Type ICollagen Type IIIDisease Models, AnimalLigationLiverLiver Cirrhosis, BiliaryLiver Cirrhosis, ExperimentalMalePiperidinesPortal PressureQuinazolinesQuinazolinonesRNA, MessengerRatsRats, WistarReverse Transcriptase Polymerase Chain Reaction