Abstract
The liver is of central importance in the metabolism of essential and toxic metals such as cadmium (Cd). Cd pretreatment suppressed the regenerative capacity of hepatocytes, which normally occurs 24 hr after partial hepatectomy, due to the inhibition of the activity of the enzyme thymidine kinase. The effect of hepatic stimulator substance (HSS) administration (10, 20, and 40 mg protein/kg body weight) on hepatocyte proliferation was investigated in Cd-pretreated partially hepatectomized rats. HSS administration partly restored the suppressed hepatocyte DNA biosynthesis in Cd-pretreated partially hepatectomized rats. The hepatocyte mitotic activity and the percentage of proliferating cell nuclear antigen-positive nuclei were in accordance with the liver proliferative status. The administration of HSS did not affect in a statistically significant manner the activity of the enzyme thymidine kinase in Cd-pretreated partially hepatectomized rats. It is suggested that the administration of HSS ameliorates the diminished hepatocyte regenerative response to partial hepatectomy in this model of acute liver injury, due to Cd intoxication.
Similar content being viewed by others
References
Michalopoulos GM: Liver regeneration: Molecular mechanisms of growth control. FASEB J 4:176–187, 1990
Kacew S, Merali Z, Thakur AN, Singhal RL: Sequential changes in hepatic polyamine, deoxyribonucleic acid, and cyclic adenosine 3′,5′-monophosphate metabolism after subacute exposure to cadmium in rats. Can J Physiol Pharmacol 155:508–514, 1977
Cihak A, Inoue H: Synthesis of DNA in the liver and testes of cadmium-treated partially hepatectomized rats. J Biochem 86:657–662, 1979
Margeli A, Theocharis S, Skaltsas S, Skopelitou A, Kittas C, Mykoniatis M, Varonos D: Effect of cadmium pretreatment on rat liver regeneration after partial hepatectomy in rats. Arch Toxicol 68:85–90, 1994
Margeli A, Theocharis S, Skaltsas S, Skopelitou A, Mykoniatis M: Effect of cadmium on rat liver regeneration after partial hepatectomy in rats. Environ Health Perspect 102(suppl 3):273–276, 1994
Waalkes MP, Goering PL: Metallothionein and other cadmium-binding proteins: recent developments. Chem Res Toxicol 3:281–288, 1990
Theocharis S, Margeli A, Giannakou N, Drakopoulos D, Mykoniatis M: Cadmium-induced hepatotoxicity in three different rat strains. Toxicol Lett 70:39–48, 1994
Theocharis S, Margeli A, Ghikonti I, Varonos D: Liver thymidine kinase activity after cadmium-induced hepatotoxicity. Toxicol Lett 63:181–190, 1992
Theocharis S, Margeli A, Alevizou V, Varonos D: Thymidine kinase activity in liver and serum of rats after cadmium administration. Toxicol Lett 71:1–7, 1994
Margeli A, Theocharis S, Yannakou N, Spiliopoulou C, Koutselinis A: Metallothionein expression during liver regeneration after partial hepatectomy in cadmium-pretreated rats. Arch Toxicol 68:637–642, 1994
Fleig WE: Liver specific growth factors. Scand J Gastroenterol 23(suppl 151):31–36, 1988
LaBrecque DR, Pesh LA: Preparation and partial characterization of hepatic regenerative stimulator substance (SS) from rat liver. J Physiol 248:273–284, 1975
Fleig WE, Lehmann H, Wagner H, Hoss G, Ditschuneit H: Hepatic regenerative stimulator substance in the rabbit. Relation to liver regeneration after partial hepatectomy. J Hepatol 3:19–26, 1986
Francavilla A, Ove P, Polimeno L, Coetzee M, Makowka L, Rose J, Van Thiel DH, Starzl TE: Extraction and partial purification of a hepatic stimulatory substance in rats, mice, and dogs. Cancer Res 47:5600–5605, 1987
Higgins GM, Anderson RM: Experimental pathology of the liver. Restoration of the liver of the white rat following partial surgical removal. Arch Pathol 12:186–201, 1931
Munro HN, Fleck A: Recent developments in the measurement of nucleic acids in biological materials. Analyst 91:78–88, 1966
Richards GM: Modifications of the diphenylamine reaction giving increased sensitivity and simplicity in the estimation of DNA. Anal Biochem 57:369–376, 1974
Kahn D, Svanas G, Eagon P, Makowka L, Podesta L, Chapchap P, Starzl T, Van Thiel D: Effect of an antiandrogenic H2 receptor antagonist on hepatic regeneration in rats. J Lab Clin Med 112:232–239, 1988
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275, 1951
International Federation of Clinical Chemistry: Committee on Standards, Enzyme Panel. Clin Chem 24:720–721, 1978
Simpson JF, Dutt PL, Page DL: Expression of mitoses per thousand cells and cell density in breast carcinomas: A proposal. Hum Pathol 23:608–611, 1992
Baak JPA, Van Dop H, Kurver PHJ, Hermans J: The value of morphometry to classic prognosticators in breast cancer. Cancer 56:374–382, 1985
Hall PA, Levison DA, Woods AL, Yu CC-W, Kellock DB, Watkins JA, Barnes DM, Gillett CE, Camplejohn R, Dover R, Wassem NH, Lane DP: Proliferating cell nuclear antigen (PCNA) immunolocalization in paraffin sections: An index of cell proliferation with evidence of deregulated expression in some neoplasms. J Pathol 162:285–294, 1990
Theocharis S, Skopelitou A, Margeli A, Pavlaki K, Kittas C: Proliferating cell nuclear antigen (PCNA) expression in regenerating rat liver after partial hepatectomy. Dig Dis Sci 39:245–252, 1994
LaBrecque DR, Feigenbaum A, Bachur NR: Diurnal rhythm: Effects on hepatic regeneration and hepatic regenerative stimulator substance. Science 199:1082–1084, 1978
LaBrecque DR, Steele G, Fogerty S, Wilson M, Barton J: Purification and physical-chemical characterization of hepatic stimulator substance. Hepatology 7:100–106, 1988
LaBrecque DR, Bachur NR: Hepatic stimulator substance: Physiochemical characteristics and specificity. Am J Physiol 242:G281-G288, 1982
Cellis JE, Bravo R, Larsen PM, Fey SJ: Cyclin: A nuclear protein whose levels correlates directly with the proliferative state of normal as well as of transformed cell. Leuk Res 8:143–157, 1984
Bravo R, MacDonald-Bravo H: Existence of two populations of cyclin/proliferating cells nuclear antigen during the cell cycle: Associations with DNA replications sites. J Cell Biol 105:1549–1554, 1987
Margeli A, Theocharis S, Skaltsas S, Spiliopoulou C, Koutselinis A: Exogenous putrescine administration ameliorates the suppressed regenerative capacity of cadmium-pretreated rat hepatocytesIn European IHPBA Congress “Athens 1995.” L. Papastamatiou (ed). Monduzzi Editore, Bologna, Italy, 1995, pp 77–81
Mao-Hua M, Wei A, Bao-Hong Z, Qing S, De-Zheng G: Hepatic stimulator substance protects against acute liver failure induced by carbon tetrachloride poisoning mice. Hepatology 17:638–644, 1993
Margeli A, Theocharis S, Spiliopoulou C, Koutselinis A: Hepatic stimulator substance administration and cadmium-induced hepatotoxicity in the rat. Pharmacol Res 31(suppl):213, 1995
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Theocharis, S.E., Margeli, A.P., Spiliopoulou, C. et al. Hepatic stimulator substance administration enhances regenerative capacity of hepatocytes in cadmium-pretreated partially hepatectomized rats. Digest Dis Sci 41, 1475–1480 (1996). https://doi.org/10.1007/BF02088575
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02088575