Hepatic stimulator substance activity in the liver of thioacetamide-intoxicated rats

Aims/Background. Hepatic stimulator substance (HSS) is a known hepatic grow th factor which appears to be organ-specific but species non-specific. We h ave recently shown that the administration of ass enhanced hepatocyte proli feration occurring due to thioacetamide (TAA)-induced liver injury in rats (Theocharis SE, et al., Scand J Gastroenterol 1998; 33: 656-63). In the pre sent study, we examined the activity of the endogenously produced ass in th e liver of TAA administered rats during injury and regeneration. Methods. T AA at a dose of 300 mg/kg of body weight was injected intraperitoneally in male Wistar rats. The animals were sacrificed at 0, 12, 24, 36, 48, 60 and 72 h after TAA administration. The rate of tritiated thymidine incorporatio n into hepatic DNA, the enzymatic activity of liver thymidine kinase and th e assessment of mitotic index in hepatocytes were used to estimate liver re generation. ass extract was obtained from the livers of TAA-treated rats, s acrificed at the above mentioned time points. This HSS extract was injected in 34% partially hepatectomized rats, to assess its activity. The ability of the injected HSS extract to increase hepatocellular proliferation over t hat normally occurring 24 h following 34% partial hepatectomy was used to e xpress the activity of HSS by determining the above mentioned indices of li ver regeneration. Results: The administration of TAA caused severe hepatic injury recognized histopathologically as well as by the increased activitie s of serum hepatic enzymes aspartate and alanine aminotransferases. The hep atic injury, which peaked at 24 and 36 h post-TAA treatment (p<0.001), was followed by hepatocyte proliferation, presenting peaks at 48 and 60 h (p<0. 001). The activity of the endogenously produced HSS from livers of TAA-trea ted rats increased at 36 h after TAA administration as well as being highly expressed at 48 and 60 h thus coinciding with the peak of hepatocyte proli feration. At other time points, HSS activity was decreased. Conclusions: Th e observed variations of HSS activity in rat liver suggest active participa tion of this growth factor in hepatocyte replication which follows toxin-in duced liver injury as a repair mechanism process.