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Metabolic zonation in thioacetamide-induced liver cirrhosis

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Summary

After TAA administration to rats a central part may be distinguished histochemically from a marginal part in most of the cirrhotic nodules. The centre is characterized by a high glycogen content and by high activity of phosphorylase, G6Pase and SDH; the maxima of which are situated around the larger blood yessels. The vasculatory periphery, however, shows moderate G6PDH-activity. The marginal parts of the nodules are poor in glycogen and possess only weak G6Pase and phosphorylase activity, whereas high SDH-and G6PDH-activity can be demonstrated here. This distribution pattern leads to the conclusion that the larger blood vessels in the centre of the nodules are themselves the terminal afferent vessels. Thus the centre of the nodule corresponds to periportal zone l, while G6PDH-activity marks the area corresponding to zone 3. The fact that the marginal parts of the nodules are marked by high SDH-but weak G6Pase-activity is interpreted as the result of a preferential arterial supply to this parenchymal part. The high G6PDH-activity of the marginal part is seen in context with the regeneration processes. In all animals single nodules could be found with a high glycogen content and extremely high G6PDH-activity. This loss of heterogeneity is interpreted as a first step in the direction of malignancy.

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References

  • Bannasch P, Hesse J, Angerer H (1974) Hepatocelluläre Glycogenose und die Genese sog. hyperplastischer Knoten in der Thioacetamid-vergifteten Rattenleber. Virchows Arch B 17:29–50

    Google Scholar 

  • Brachet J (1959) Ribonucleinsäure und Morphogenese. In: Graumann W, Neumann K (eds). Handb Histochem, Bd III/2. Gustav Fischer Verlag, Stuttgart

    Google Scholar 

  • Brodehl J (1961) Thioacetamid in der experimentellen Leberforschung. Klin Wochenschr 18:956–962

    Google Scholar 

  • Chenderovitch J, Caroli J (1956) La microangioradiographie du foie et de la rate. Rev Int Hepatol 6:907–977

    Google Scholar 

  • Childs JFL, Siegler EA (1945) Compounds for control of orange decays. Science 102:68

    Google Scholar 

  • Chiquoine AD (1953) The distribution of glucose-6-phosphatase in the liver and kidney of the mouse. J Histochem Cytochem 1:429–439

    Google Scholar 

  • Date PA, Bhide SV (1973) Mechanism of thioacetamide action: specific effect of thioacetamide and acetamide on glycogen levels. Indian J Exp Biol 11:327–329

    Google Scholar 

  • Eder M, Butenandt O, Josten R (1965) Morphologische, histochemische und autoradiographische Untersuchungen zur akuten und chronischen Thioacetamid-Vergiftung. Frankf Z Pathol 74:599–619

    Google Scholar 

  • Fitzhugh OG, Nelson AA (1948) Liver tumors in rats fed thiourea or thioacetamide. Science 108:626–628

    Google Scholar 

  • Gallagher CH, Gupta DN, Judah JD, Rees KR (1956) Biochemical changes in liver in acute thioacetamide intoxication. J Pathol Bacteriol 72:193–201

    Google Scholar 

  • Glock GE, McLean P (1953) Further studies on the properties and assay of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase of rat liver. Biochem J 55:400–408

    Google Scholar 

  • Goebel A, Puchtler H (1955) Untersuchungen zur Methodik der Darstellung der Succinodehydrogenase im histologischen Schnitt. Virchows Arch Pathol Anat Physiol 326:312–331

    Google Scholar 

  • Graumann W (1953) Zur Standardisierung des Schiffschen Reagens. Z Wiss Mikrosk 61:225–226

    Google Scholar 

  • Grisham JW (1959) Lobular distribution of hepatic nuclei labeled with tritiated-thymidine in partially hepatectomized rats. Fed Proc 18:478

    Google Scholar 

  • Grisham JW (1960) Deoxyribose nucleic acid synthesis and cell renewal in regenerating rat liver. J Histochem Cytochem 8:330

    Google Scholar 

  • Guder WG, Schmidt U (1976) The distribution of pyruvate kinase and phosphoenolpyruvate carboxykinase in the liver lobule of fed and starved rats. Hoppe Seylers Z Physiol Chem 357:1793–1800

    Google Scholar 

  • Gupta DN (1955) Production of cancer of the bile ducts with thioacetamide. Nature 175:257

    Google Scholar 

  • Gupta DN (1956) Nodular cirrhosis and metastasising tumors produced in the liver of rats by prolonged feeding with thioacetamide. J Pathol Bacteriol 72:415–426

    Google Scholar 

  • Hagemann E (1959) Experimentelle Lebercirrhose bei Ratten nach Thioacetamid. Zentralbl Allg Pathol Pathol Anat 99:100

    Google Scholar 

  • Hori SH, Matsui S (1967) Effects of Hormones on hepatic glucose-6-phosphate dehydrogenase of rat. J Histochem Cytochem 15:530–534

    Google Scholar 

  • Hruban Z, Gradman W, Slesers A, Lubran M (1966) Toxicity of thioacetamide. Lab Invest 15:1748–1760

    Google Scholar 

  • Huggins C, Yao FO (1959) Influence of hormones on liver. J Exp Med 110:899–919

    Google Scholar 

  • Jungermann K, Sasse D (1978) Heterogeneity of liver parenchymal cells. Trends Biochem Sci 3:198–202

    Google Scholar 

  • Karl HJ, Wiedemann M, Raith L (1971) Produktion und Stoffwechsel von Corticosteroiden und Androgenen bei der Lebercirrhose. Klin Wochenschr 49:340–345

    Google Scholar 

  • Katz N, Teutsch HF, Sasse D, Jungermann K (1977) Heterogeneous distribution of glucose-6-phosphatase in microdissected periportal and perivenous rat liver tissue. FEBS Lett 76:226–230

    Google Scholar 

  • Kleinfeld RG (1957) Early changes in rat liver and kidney cells induced by thioacetamide. Cancer Res 17:954–962

    Google Scholar 

  • Kullmann R, Kiefer G, Sandritter W (1971) Experimentelle Beeinflussung des Ribonukleinsäuregehaltes der Rattenleber durch Thioacetamid. Beitr Pathol 143:1–13

    Google Scholar 

  • Lourens J (1973) Geslachtshormonen en levercirrhose.Inaugural dissertation University of Utrecht

  • McManus JFA (1948) Histological and histochemical uses of periodic acid. Stain Technol 23:99–108

    Google Scholar 

  • Moschcowitz E (1948) Laennec cirrhosis: its histogenesis, with special reference to the role of angiogenesis. Arch Pathol 45:187–215

    Google Scholar 

  • Peterson R (1960) Adrenocortical steroid metabolism and adrenal cortical function in liver disease. J Clin Invest 39:320–331

    Google Scholar 

  • Popper H, Elias H, Petty DE (1952) Vascular pattern of the cirrhotic liver. Am J Clin Pathol 22:717–729

    Google Scholar 

  • Popper H, Schaffner F (1961) Die Leber, Struktur und Funktion. Thieme, Stuttgart

    Google Scholar 

  • Rappaport AM (1963) Acinar units and the pathophysiology of the liver. In: Rouiller C (ed). The liver, Bd I. Academic Press, New York

    Google Scholar 

  • Rappaport AM (1976) The microcirculatory acinar concept of normal and pathological hepatic structure. Beitr Pathol 157:215–243

    Google Scholar 

  • Reddy JK, Rao MS, Jago MV (1976) Rapid development of hyperplastic nodules and cirrhosis in the liver of rats treated concurrently with thioacetamide and pyrrolizidine alkaloid lasiocarpine. Int J Cancer 17:621–625

    Google Scholar 

  • Rieder H, Teutsch HF, Sasse D (1978) NADP-dependent dehydrogenases in rat liver parenchyma. Methodological studies on the qualitative histochemistry of G6PDH, 6PGDH, malic enzyme and ICDH. Histochemistry 56:283–298

    Google Scholar 

  • Sasse D (1975) Dynamics of liver glycogen. The topochemistry of glycogen synthesis, glycogen content and glycogenolysis under the experimental conditions of glycogen accumulation and depletion. Histochemistry 45:237–254

    Google Scholar 

  • Sasse D, Katz N, Jungermann K (1975) Functional heterogeneity of rat liver parenchyma and of isolated hepatocytes. FEBS Lett 57:83–88

    Google Scholar 

  • Schepers GWH (1961) Hepatic cellular gigantism as a manifestation of chemical toxicity.U.S. Executive Committee 13th Int Congr on Occupational Health, New York

  • Schmidt U, Schmidt H, Guder WG (1978) Liver cell heterogeneity. The distribution of fructosebisphosphatase in fed and fasted rats and in man. Hoppe Seylers Z Physiol Chem 359:193–198

    Google Scholar 

  • Schumacher HH (1957) Histochemical distribution pattern of respiratory enzymes in the liver lobule. Science 125:501–503

    Google Scholar 

  • Schwietzer CH, Schaetz G (1957) Die Erzeugung experimenteller Lebercirrhose durch Thioacetamid. In: Kühn HA (Hrsg) Pathologie, Diagnostik und Therapie der Leberkrankheiten. Springer, Berlin Göttingen Heidelberg

    Google Scholar 

  • Takeuchi T, Kuriaki H (1955) Histochemical detection of phosphorylase in animal tissues. J Histochem Cytochem 3:153–160

    Google Scholar 

  • Teutsch HF (1978) Improved method for the histochemical demonstration of glucose-6-phosphatase activity. Histochemistry 56:107–117

    Google Scholar 

  • Teutsch HF (1978) Quantitative determination of glucose-6-phosphatase activity in histochemically defined zones of the liver acinus. Histochemistry 58:281–288

    Google Scholar 

  • Teutsch HF, Rieder H (1979) NADP-dependent dehydrogenases in rat liver parenchyma. II. Comparison of qualitative and quantitative G6PDH distribution patterns with particular reference to sex differences. Histochemistry 60:43–52

    Google Scholar 

  • Thijssen JHH, Lourens J, Donker GH (1971) Androstenedione and testosterone production and interconversion rates measured in peripheral blood in male patients with cirrhosis of the liver. Acta Endocrinol (Kbh) Suppl 155:116

    Google Scholar 

  • Thijssen JHH, Lourens J, Donker GH, Schwarz F (1975) The role of the liver in the biogenesis of oestrogens in cirrhosis of the liver. Acta Endocrinol (Kbh) Suppl 199:234

    Google Scholar 

  • Thoenes W, Bannasch P (1962) Elektronen-und lichtmikroskopische Untersuchungen am Cytoplasma der Leberzellen nach akuter und chronischer Thioacetamid-Vergiftung. Virchows Arch Pathol Anat 335:556–583

    Google Scholar 

  • Wachstein M, Meisel E (1956) On the histochemical demonstration of glucose-6-phosphatase. J Histochem Cytochem 4:592

    Google Scholar 

  • Wachstein M, Meisel E, Falcon C (1962) Enzymatic histochemistry in the experimentally damaged liver. Am J Pathol 40:219–241

    Google Scholar 

  • Zeiger K (1952) Zur funktionellen Anatomie der Leber. Dtsch Z Verdau Stoffwechselkr Sonderbd 22–31

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Dedicated to Prof. Dr. W. Graumann on the occasion of his 65th birthday

Supported by a grant from the Deutsche Forschungsgemeinschaft (Sa 127/7)

The essential part of this study was presented as an Inaugural Dissertation to the Medical Faculty of the University of Freiburg by R. Nuber

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Nuber, R., Teutsch, H.F. & Sasse, D. Metabolic zonation in thioacetamide-induced liver cirrhosis. Histochemistry 69, 277–288 (1980). https://doi.org/10.1007/BF00489773

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