Co-Authors:
Spira, G., Department of Anatomy and Cell Biology, The Bruce Rappaport Fac. of Med., Rappaport Fam. Inst. for Res. in the Medical Sciences, Technion, Haifa, Israel
Mawasi, N., Department of Anatomy and Cell Biology, The Bruce Rappaport Fac. of Med., Rappaport Fam. Inst. for Res. in the Medical Sciences, Technion, Haifa, Israel
Paizi, M., Department of Anatomy and Cell Biology, The Bruce Rappaport Fac. of Med., Rappaport Fam. Inst. for Res. in the Medical Sciences, Technion, Haifa, Israel
Anbinder, N., Department of Anatomy and Cell Biology, The Bruce Rappaport Fac. of Med., Rappaport Fam. Inst. for Res. in the Medical Sciences, Technion, Haifa, Israel
Genina, O., Institute of Animal Sciences, Agriculture Research Organization, the Volcani Center, Bet Dagan, Israel
Alexiev, R., Institute of Animal Sciences, Agriculture Research Organization, the Volcani Center, Bet Dagan, Israel
Pines, M., Institute of Animal Sciences, Agriculture Research Organization, the Volcani Center, Bet Dagan, Israel
Abstract:
Background/Aims: Hepatic fibrosis involves excess deposition of extracellular connective tissue of which collagen type I fibers form the predominant component. Left untreated it develops into cirrhosis, often linked with hepatocellular carcinoma. Owing to the fact that cirrhotic liver regeneration is impaired, resection of hepatocellular carcinoma associated with cirrhosis is questionable. The aim of the present study was to determine the potential of halofuginone, a collagen type I inhibitor, in improving liver regeneration in cirrhotic rats. Methods: Partial hepatectomy (70%) was performed in thioacetamide-induced cirrhotic rats fed a halofuginone-containing diet. Liver regeneration was monitored by mass and proliferating cell nuclear antigen. The Ishak staging system and hydroxyproline content were used to evaluate the level of fibrosis. Results: Halofuginone administered prior to and following partial hepatectomy did not inhibit normal liver regeneration despite the reduced levels of collagen type I mRNA. When given to rats with established fibrosis, it caused a significant reduction in α smooth muscle actin, TIMP-2, collagen type I gene expression and collagen deposition. Such animals demonstrated improved capacity for regeneration. Conclusions: Halofuginone may prove useful in improving survival of patients with hepatocellular carcinoma and cirrhosis undergoing surgical resection. © 2002 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.
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