Abstract
Metallothionein is a low molecular mass protein inducible mainly by heavy metals, having high affinity for binding cadmium, zinc and copper. In the present study we investigated the expression of metallothionein in regenerating liver, at different time intervals, in cadmium pretreated partially hepatectomized rats. Liver metallothionein is highly expressed during regeneration in-duced by partial hepatectomy in rats, providing zinc within the rapidly growing tissue. Cadmium pretreatment caused inhibition of the first peak of liver regeneration, while metallothionein expression was markedly more prominent in the liver residues of cadmium-pretreated rats. These results demonstrate that although metallothionein able to bind temporarily metal ions as zinc and cadmium has been highly expressed, the liver regenerative process was inhibited possibly due to the effects of cadmium on other pivotal events necessary to the DNA replication.
Similar content being viewed by others
References
Akerman P, Cote P, Qi Yang S, McClain C, Nelson S, Bagby G, Mae Diehl A (1992) Antibodies to tumor necrosis factor-α inhibit liver regeneration after partial hepatectomy. Am J Physiol 263: G579-G585
Brady F (1982) The physiological function of metallothionein. Trends Biochem Sci 7: 143–145
Cain K, Griffiths B (1984) A comparison of isometallothionein synthesis in rats after partial hepatectomy and parenteral zinc injection. Biochem J 217: 85–92
Cornell RP (1990) Acute phase responses after acute liver injury by partial hepatectomy in rats as indicators of cytokine release. Hepatology 11: 923 - 931
Cousins RJ, Leinart AS (1988) Tissue specific regulation of zinc metabolism and metallothionein genes by interleukin-I. FASEB J 2: 2884–2890
Di Silvestro RA, Cousins RJ (1984) Glucocorticoid independent mediation of interleukin-l induced changes in serum zinc and liver metallothionein levels. Life Sci 35: 2113 -2118
Dudley R, Svoboda D, Klaassen C (1982) Acute exposure to cadmium causes severe liver injury in rats. Toxicol Appl Pharmacol 65: 302–313
Hambridge KM, Casey CE, Krebs NF (1986) Zinco In: Mertz W (ed) Trace elements in human and animal nutrition, 5th edition. Academic Press Inc, New York, pp 1–137
Higgins G, Anderson R (1931) Experimental pathology of liver. I. Restoration of liver of the white rat following partial surgical removal. Arch Pathol 12: 186–201
Kagi JHR, Vasak M, Lerch K, Gilg DEO, Hunzika P, Bernhard WR, Good M (1984) Structure of metallothionein. Environ Health Perspect 54: 93–104
Kahn D, StadIer J, Terblanche J, Van Hoorn-Hickman R (1980) Thymidine kinase: an inexpensive index of liver regeneration in a large animal model. Gastroenterology 79: 907 -911
Kahn D, Svanas G, Eagopn P, Makowka L, Podesta L, Chapchap P, Starzl T, Van Thiel D (1988) Effect of an antiandrogenic H2 receptor antagonist on hepatic regeneration in rats. J Lab Clin Med 112: 232–239
Klug A, Rhodes D (1987) Zinc fingers: a novel protein motif for nucleic acid regulation. Trends Biochem Sci 12: 464–469
Koga M, Ogasawara H (1991) Induction of hepatocyte mitosis in intact adult rat by interleukin-1α and interleukin-6. Life Sci 49: 1263–1270
Lowry O, Rosenbrough N, Farr A, Randal R (1951) Protein measurement with folin reagent. J Biol Chem 193: 265–275
Maitani T, Waalkes MP, Klaassen CD (1984) Distribution of cadmium after oral administration of cadmium-thionein to mice. Toxicol Appl Pharmacol 74: 237 -243
Margeli A, Theocharis S, Skaltsas S, Skopelitou A, Kittas C, Mykoniatis M, Varonos D (1994a) Effect of cadmium pretreatment on liver regeneration after partial hepatectomy in rats. Arch Toxicol 68: 85–90
Margeli A, Theocharis S, Skaltsas S, Skopelitou A, Mykoniatis M (1994b) Effect of cadmium on liver regeneration after partial hepateetomy in rats. Environ Health Perspect (in press)
Margoshes M, Valle BC (1957) A cadmium protein for equine kidney cortex. J Am Chem Soc 79: 4813–4814
Michalopoulos GM (1990) Liver regeneration: molecular mechanisms of growth control. FASEB J 4: 176–187
Munro H, Heck A (1966) Recent developments in the measurement of nucleic acids in biological materials. Analyst 91: 78–88
Ohtake H, Koga M (1979) Purification and characterization of zincbinding protein from the liver of the partially hepatectomized rat. Biochem J 183: 683–690
Ohtake H, Hasegawa K, Koga M (1978) Zinc binding protein in livers of neonatal, nonnal and partially hepatectomized rats. Biochem J 174: 999–1005
Otvos JD, Armitage IM (1980) Structure of the metal clusters in rabbit liver metallothionein. Proc Natl Acad Sci USA 77: 7094–7098
Piscator M (1964) On cadmium in normal human kidneys together with a report on the isolation of metallothionein for livers of cadmium exposed rabbits. Nord Hyg 45: 76–82
Richards G (1974) Modifications of the diphenylamine reaction giving increased sensitivity and simplicity in the estimation of DNA. Anal Biochem 57:369–376
Smith JC Jr, Butrimovitz GP, Purdy WC (1979) Direct measurement of zinc in plasma by atomic absorption spectroscopy. Clin Chem 25: 1487
Theocharis S, Margeli A, Fasitsas C, Loizidou M, Deliconstantinos G (1991) Acute exposure to cadmium causes time-dependent liver injury in rats. Comp Biochem Physiol 99C: 127–130
Theocharis S, Margeli A, Ghiconti I, Varonos D (1992) Liver thymidine kinase activity after eadmium-induced hepatotoxicity in rats. Toxicol Lett 63: 181–190
Theocharis S, Margeli A, Giannakou N, Drakopoulos D, Mykoniatis M (1994a) Cadmium-induced hepatotoxicity in three different rat strains. Toxicol Lett 70: 39–48
Theocharis S, Margeli A, Alevizou V, Varonos D (1994b) Thymidine kinase activity in liver and serum of rats after cadmium administration. Toxicol Lett 71: 1–7
Tohyama C, Suzuki J, Hemelraad J, Nishimura N, Nishimura H (1993) Induction of metallothionein and its localization in the nucleus of rat hepatocytes after partial hepatectomy. Hepatology 18: 1193 -1201
Tsukamoto I, Kojo S (1987) One evidence supporting that thymidylate synthetase and thymidine kinase are the rate-determining enzymes of DNA synthesis in regenerating rat Iiver. Chem Lett 12: 2313–2316
Waalkes M, Ward J (1989) Induction of Hepatic metallothionein in male B6C3F1 mice exposed to hepatic tumor promoters: effects of phenobarbital, acetaminophen, sodium barbital and di(2-ethylhexyl) phthalate. Toxicol Appl Pharmacol 100: 217–226
Waalkes M, Goering P (1990) Metallothionein and other cadmiumbinding proteins: recent developments. Chem Res Toxicol 3[4]: 281–288
Wong K, Klaassen C (1979) Isolation and characterization of metallothionein which is highly concentrated in newborn rat liver. J Biol Chem 254: 12399–12403
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Margeli, A.P., Theocharis, S.E., Yannacou, N.N. et al. Metallothionein expression during liver regeneration after partial hepatectomy in cadmium-pretreated rats. Arch Toxicol 68, 637–642 (1994). https://doi.org/10.1007/BF03208343
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF03208343