Hepatic stimulator substance administration ameliorates liver regeneration in an animal model of fulminant hepatic failure and encephalopathy.
OBJECTIVE
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.
Margeli
Alexandra P
AP
Department of Experimental Pharmacology, University of Athens, Medical School, Department of Clinical Biochemistry, Aghia Sophia Children's Hospital, Athens, Greece.
Papadimitriou
Lila
L
Ninos
Sotirios
S
Manolis
Evangelos
E
Mykoniatis
Michael G
MG
Theocharis
Stamatios E
SE
D000818:Animals; D006133:Growth Substances / Q000008:administration & dosage*; D006501:Hepatic Encephalopathy / Q000139:chemically induced; D007274:Injections, Intraperitoneal; D036341:Intercellular Signaling Peptides and Proteins; D017093:Liver Failure / Q000139:chemically induced*; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D008934:Mitogens / Q000008:administration & dosage*; D023421:Models, Animal; D010455:Peptides / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D013457:Sulfur Compounds / Q000009:adverse effects; D016019:Survival Analysis; D013853:Thioacetamide / Q000009:adverse effects
D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D008934:Mitogens; D010455:Peptides; D013457:Sulfur Compounds; C073456:hepatic stimulator substance; D013853:Thioacetamide