title: Hepatic stimulator substance activity in animal model of fulminant hepatic failure and encephalopathy.
abstract: Hepatic stimulator substance (HSS) is a known liver-specific but species-nonspecific growth factor. In the present study we examined the activity of the endogenously produced HSS in an established experimental model of fulminant hepatic failure (FHF) and encephalopathy, induced by repeated injections of thioacetamide (TAA). FHF was induced by three consecutive intraperitoneal injections of TAA (400 mg/kg body weight) in rats, at time intervals of 24 hr. The animals were killed at 0, 6, 12, or 18 hr following the last injection of TAA. The rate of tritiated thymidine incorporation into hepatic DNA, the enzymatic activity of liver thymidine kinase (EC 2.7.1.21), and the assessment of mitotic index in hepatocytes were used to estimate liver regeneration. HSS extract obtained from the livers of TAA-treated rats, sacrificed at the above-mentioned time points was tested for its activity. Increased HSS activity was noted in all TAA-treated animals, presenting a peak at 12 hr following the third TAA dose, suggesting active participation of this growth factor in hepatocyte replication in this animal model of FHF and encephalopathy. It may also be suggested that up-regulation of HSS activity could be used in future as a therapeutic approach in FHF.
authors.affiliation: Department of Experimental Pharmacology, Medical School, University of Athens, Greece.
authors.forename: Alexandra P
authors.initials: AP
authors.lastname: Margeli
authors.forename: Evangelos
authors.initials: E
authors.lastname: Manolis
authors.forename: Spyridon N
authors.initials: SN
authors.lastname: Skaltsas
authors.forename: Kyriakos S
authors.initials: KS
authors.lastname: Tsarpalis
authors.forename: Michael G
authors.initials: MG
authors.lastname: Mykoniatis
authors.forename: Stamatios E
authors.initials: SE
authors.lastname: Theocharis
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006133:Growth Substances / Q000378:metabolism*; D006501:Hepatic Encephalopathy / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D007274:Injections, Intraperitoneal; D036341:Intercellular Signaling Peptides and Proteins; D008099:Liver / Q000473:pathology / Q000503:physiopathology; D017093:Liver Failure / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D008111:Liver Function Tests; D008115:Liver Regeneration / Q000502:physiology; D008297:Male; D009336:Necrosis; D010455:Peptides / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013853:Thioacetamide / Q000633:toxicity; D015854:Up-Regulation / Q000502:physiology
chemical_list: D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; C073456:hepatic stimulator substance; D013853:Thioacetamide