Hepatic stimulator substance administration ameliorates liver regeneration in an animal model of fulminant hepatic failure and encephalopathy
Article first published online: 7 MAY 2003
Volume 23, Issue 3, pages 171–178, June 2003
How to Cite
Margeli, A. P., Papadimitriou, L., Ninos, S., Manolis, E., Mykoniatis, M. G. and Theocharis, S. E. (2003), Hepatic stimulator substance administration ameliorates liver regeneration in an animal model of fulminant hepatic failure and encephalopathy. Liver International, 23: 171–178. doi: 10.1034/j.1600-0676.2003.00828.x
- Issue published online: 7 MAY 2003
- Article first published online: 7 MAY 2003
- Received 2 October 2002, accepted 10 February 2003
- fulminant hepatic failure;
- hepatic stimulator substance;
- liver injury;
- hepatic encephalopathy;
- liver regeneration
Abstract: Aims/Background: Hepatic stimulator substance (HSS) is a liver-specific growth factor implicated in hepatocellular proliferation and hepatoprotection in models of acute liver injury. In the present study, we examined the effect of exogenous HSS administration on liver proliferating capacity and survival outcome in an experimental animal model of fulminant hepatic failure (FHF) and encephalopathy, induced by repeated injections of thioacetamide (TAA) in rats.
Methods: Fulminant hepatic failure was induced in adult male Wistar rats by three consecutive intraperitoneal injections of TAA (400 mg/kg of body weight), at 24 h time intervals. The animals received intraperitoneally either a saline solution or HSS (50 mg protein/kg of body weight), 2 h after the second and third TAA injections. The animals were killed at 6, 12 and 18 h post the last injection of TAA.
Results: Levels of liver enzymes and urea in serum, blood ammonia values, liver histology, stage of hepatic encephalopathy and survival were statistically significantly improved in TAA-intoxicated and HSS-treated rats compared to TAA-intoxicated and saline-treated ones. Furthermore, HSS ameliorated liver regenerative indices – DNA biosynthesis, thymidine kinase activity and hepatocyte mitotic activity – in a statistically significant manner.
Conclusions: Our data suggest the beneficial effect of HSS administration in this animal model of FHF and encephalopathy, supporting evidence for a possible use of HSS as supportive therapy, by increasing hepatocellular proliferation, in management of FHF.