The role of hepatic stimulator substance (HSS) on liver regeneration arrest induced by cadmium

In Vivo. 2005 Jul-Aug;19(4):695-704.


Background: The mechanism of cadmium-induced liver regeneration arrest in relation to hepatic stimulator substance (HSS) biological activity was investigated.

Materials and methods: In Wistar rats subjected to 65 - 70% partial hepatectomy, saline, cadmium, cadmium and HSS were administered. The rats were also subjected to 30 - 34% partial hepatectomy. Mitotic index, immunochemistry for PCNA, 3[H]-thymidine incorporation into DNA and thymidine kinase activity were used as indices of liver regeneration. HSS biological activity was evaluated in all groups of rats using a bioassay.

Results: Liver regeneration and HSS activity were arrested by cadmium during the first 24 h after partial hepatectomy. Both in normal and in cadmium-treated rats, the HSS activity was increased and liver regeneration coincided. HSS activity was stable in 30 - 34% hepatectomized rats. HSS administration was able to restore liver regeneration arrest induced by cadmium.

Conclusion: The biological activity of HSS increased at the time of G1/S transition of hepatocytes in the cell cycle and no increase was observed with asynchronous G1/S transition (30 - 34% partial hepatectomy). The suppression of HSS biological activity by cadmium seems to represent an important factor for liver regeneration arrest induced by the metal and HSS administration is able to restore liver regeneration.

MeSH terms

  • Animals
  • Cadmium / toxicity*
  • DNA / biosynthesis
  • DNA / drug effects
  • Growth Substances / metabolism*
  • Growth Substances / pharmacology
  • Hepatectomy
  • Immunohistochemistry
  • Injections, Intraperitoneal
  • Intercellular Signaling Peptides and Proteins
  • Liver / drug effects
  • Liver / enzymology
  • Liver / pathology
  • Liver Regeneration / drug effects*
  • Male
  • Mitogens / metabolism*
  • Mitogens / pharmacology
  • Mitotic Index
  • Peptides / metabolism*
  • Peptides / pharmacology
  • Proliferating Cell Nuclear Antigen / metabolism
  • Rats
  • Rats, Wistar
  • Thymidine Kinase / drug effects
  • Thymidine Kinase / metabolism


  • Growth Substances
  • Intercellular Signaling Peptides and Proteins
  • Mitogens
  • Peptides
  • Proliferating Cell Nuclear Antigen
  • hepatic stimulator substance
  • Cadmium
  • DNA
  • Thymidine Kinase