Skip to main content
Log in

Subcellular distribution of phospholipids during liver damage induced by rare earths

  • Original Investigations
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

After intravenous injection of praseodymium nitrate, female Wistar rats develop fatty livers. In contrast to the marked increase of triglycerides, the phospholipid content was only increased by 50%. The subcellular distribution of phospholipids showed that major changes occur in the microsomal fraction within the first 24hrs. Among the individual phospholipids only phosphatidylcholine and phosphatidylethanolamine concentrations were elevated. Further subfractioning revealed that phospholipid concentration increased in the smooth endoplasmic reticulum, whereas it decreased in the rough endoplasmic reticulum. The individual phospholipids in the smooth endoplasmic reticulum increased to the same degree as did the total phospholipids. On the other hand, in the rough endoplasmic reticulum only the lecithin fraction decreased, while all other phospholipids remained unchanged. Cytochrome P450, cytochrome b5, and glucose 6-phosphatase activity were drastically reduced in the rough endoplasmic reticulum, while no changes could be observed in the smooth endoplasmic reticulum.

In the serum, phospholipid concentration fell to half the normal value within the first 24 hrs after praseodymium intoxication.

Zusammenfassung

Die Injektion von Praseodymnitrat führt bei weiblichen Wistar-Ratten zu einer ausgeprägten Leberverfettung. Im Gegensatz zur massiven Triglyceridakkumulation steigt die Phospholipid-Konzentration nur um 50 % an. Untersuchungen über die subcelluläre Verteilung der Phospholipide zeigten, daß die größten Veränderungen innerhalb der ersten 24 h nach Gabe von Praseodym in der Mikrosomenfraktion auftreten, wobei lediglich die Konzentrationen von Phosphatidylcholin und Phosphatidyläthanolamin ansteigen. Die Auftrennung der Mikrosomenfraktion in rauhes und glattes endoplasmatisches Reticulum ergab einen Anstieg der Gesamtphospholipide im glatten, dagegen einen Abfall im rauhen endoplasmatischen Reticulum. Der Anstieg der Phospholipide im glatten endoplasmatischen Reticulum beruht im wesentlichen auf einem Anstieg von Phosphatidylcholin, Phosphatidyläthanolamin und Phosphatidylinositol, während der Abfall im rauhen endoplasmatischen Reticulum nur durch eine Senkung der Phosphatidylcholin-Konzentration bedingt ist. Die Aktivitäten von Cytochrom P450, Cytochrom b5 und Glucose-6-phosphatase sind im rauhen endoplasmatischen Reticulum stark vermindert, im glatten dagegen unverändert. Im Serum kommt es 24 h nach Gabe von Praseodym zu einer Abnahme der Phospholipid-Konzentration um etwa 50 %.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Adelman, M. R., Blobel, G., Sabatini, D. D.: In: Methods in Enzymology, Vol. XXXI, Part A, (Ed. S. Fleischer), p. 201 ff. New York: Academic Press 1974

    Google Scholar 

  • Anderson, C. E., Müller, B., Yarbro, C. L., Kyker, G. C.: Rat liver lipids in rare earth induced fatty infiltration. Fed. Proc. 18, 181–189 (1959)

    Google Scholar 

  • Arvela, P.: The effect of α-tocopherol on cerium-induced changes in drug and lipid metabolism of rat. Experientia (Basel) 30, 1061–1062 (1974)

    Google Scholar 

  • Arvela, P., Kärki, N. T.: The effect of phenobarbital on the cerium induced impairment of drug metabolism in rat. Acta Pharmacol. Toxicol. 31, 380–386 (1972)

    Google Scholar 

  • Arvela, P., Kärki, N. T.: In vivo effects of cerium on lipid peroxidation and drug oxydating monoxygenase system in rat liver. 16th Meeting Soc. for the Study of Drug Toxicity, Karlsbad 1974 (in press)

  • Baginski, E. S., Foa, P. P., Zak, B.: In: Methoden der enzymatischen Analyse. 2. Aufl., (Hrsg. H.-U. Bergmeyer), S. 839–843. Weinheim: Verlag Chemie 1970

    Google Scholar 

  • Bass, R.: Untersuchungen zur Reindarstellung enzymatisch aktiver Zellfraktionen aus Warmblütergeweben. Inaugural-Diss. Med. Fak. Freie Univ. Berlin 1967

    Google Scholar 

  • Bassi, M.: Electronmicroscopy of rat liver after CCl4 poisoning. Exp. Cell Res. 20, 313–323 (1960)

    Google Scholar 

  • Bergstrand, A., Dallner, G.: Isolation of rough and smooth microsomes from rat by means of a commercially available centrifuge. Analyt. Biochem. 29, 351–359 (1969)

    Google Scholar 

  • Bruce, D. W., Hietbrink, B. E., DuBois, K. P.: The acute mammalian toxicity of rare-earth nitrates and oxides. Toxicol. appl. Pharmacol. 5, 750–759 (1963)

    Google Scholar 

  • Chance, B., Pappenheimer, A. M.: Kinetic and spectrophotometric studies of cytochrome b5 in midgut homogenates of cecropia. J. biol. Chem. 209, 931–943 (1954)

    Google Scholar 

  • Chaplin, M. D., Mannering, G. J.: Role of phospholipids in the hepatic microsomal drugmetabolizing system. Molec. Pharmacol. 6, 631–640 (1970)

    Google Scholar 

  • Cornatzer, W. E., Walser, A. H.: Biosynthesis of liver phospholipids during the development of a fatty liver. Proc. Soc. exp. Biol. (N.Y.) 116, 893–897 (1969)

    Google Scholar 

  • Creasey, W. A., Hankin, L., Handschumacher, R. E.: Fatty livers induced by orotic acid. J. biol. Chem. 236, 2064–2070 (1961)

    Google Scholar 

  • Eriksson, L. C.: Studies on the biogenesis of endoplasmic reticulum in the liver cell. Acta Path. microbiol. scand. Sec. A, Suppl. 239 (1973)

  • Fex, G.: The metabolism of liver and plasma lipids after partial hepatectomy in the rat. Biochim. biophys. Acta (Amst.) 202, 415–425 (1970)

    Google Scholar 

  • Fischler, F., Roeckl, K. W.: Über experimentelle Beeinflussung der Leberfunktion und der anatomischen Leberstruktur durch Einwirkung seltener Erden. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 189, 4–21 (1938)

    Google Scholar 

  • Folch, J., Lees, M., Stanley, G. H. S.: A simple method for the isolation and purification of total lipids from animal tissues. J. biol. Chem. 226, 497–509 (1957)

    Google Scholar 

  • Gallenkamp, H., Brachtel, D., Richter, E.: Influence of galactosamine hydrochloride on microsomal phospholipid-, protein- and cytochrome P-450 content in guinea pig liver. Acta hepato-gastroenterol. 21, 101–106 (1974)

    Google Scholar 

  • Gershbein, L. L., Singh, E. J.: Hepatic lipid changes during liver regeneration in the rat. Acta hepato-splenol. (Stuttg.) 17, 307–323 (1970)

    Google Scholar 

  • Gurr, M. I., Finean, J. B., Hawthorne, J. N.: Phospholipids of liver cell fraction. I. Phospholipid composition of liver cell nucleus. Biochim. biophys. Acta (Amst.) 70, 406–416 (1963)

    Google Scholar 

  • Hartmann, F.: Zur Pathologie der Fettleber. Acta hepato-splenol. (Stuttg.) 10, 3–18 (1963)

    Google Scholar 

  • Holtzmann, J. L., Gilette, J. R.: The effect of phenobarbital on the turnover of microsomal phospholipids in male and female rats. J. biol. Chem. 243, 3020–3030 (1968)

    Google Scholar 

  • Horning, M. G., Earle, M. J., Maling, H. M.: Changes in fatty acid composition of liver lipids induced by carbon tetrachloride and ethionine. Biochim. biophys. Acta (Amst.) 56, 175–177 (1962)

    Google Scholar 

  • Lehmann, B. v., Oberdisse, E.: Subcelluläre Verteilung von Phospholipiden nach experimenteller Leberschädigung durch Praseodym. Naunyn-Schmiedebergs Arch. Pharmacol. 282, R56 (1975)

    Google Scholar 

  • Lowry, O. H., Rosebrough, N. J., Farr, A. L., Randall, R. J.: Protein measurement with the folin phenol reagent. J. biol. Chem. 193, 265 (1951)

    Google Scholar 

  • Magnusson, G.: The behaviour of certain lanthanons in rats. Acta pharmacol. (Kbh.) 3Suppl.3, 1–95 (1963)

    Google Scholar 

  • Maibauer, D., Neubert, D., Rottka, H.: Pharmakologische Untersuchungen bei der experimentellen Leberverfettung. Naunyn-Schmiederbergs Arch. exp. Path. Pharmak. 234, 474–489 (1958)

    Google Scholar 

  • Miller, J. E., Cornatzer, W. E.: Studies on liver phosphatidylcholines. I: Effects of fatty liver induction on phosphatidylcholines from mitochondria and microsomes. Lipids 4, 19–27 (1969)

    Google Scholar 

  • Neubert, D., Hoffmeister, I.: Intrazelluläre Lokalisation von Fettsubstanzen bei experimenteller Leberverfettung. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 237, 519–537 (1960)

    Google Scholar 

  • Oberdisse, E., Winkler, R., Grajewski, O., Lehmann, B. v., Arntz, H. R.: Pharmakologische Untersuchungen zum Mechanismus der Praseodym ausgelösten Leberschädigung. Verh. dtsch. Ges. inn. Med. 80, 1556–1558 (1974)

    Google Scholar 

  • Omura, T., Sato, R.: The carbon monoxide-binding pigment of liver microsomes. I. Evidence for its hemoprotein nature. J. biol. Chem. 239, 2370–2378 (1964)

    Google Scholar 

  • Peter, H. W., Wolf, U.: A new method for the in situ determination of phospholipids after thinlayer separation. The phospholipid content of Ca-ATPase and Na,K-ATPase from human erythrocyte in comparison with phospholipid content of human erythrocytes. J. Chromatography 82, 15–30 (1973)

    Google Scholar 

  • Recknagel, R. O., Glende, E. A., Ugazio, G., Koch, R. R., Srinivasan, S.: New data in support of the lipoperoxidation theory for carbontetrachloride liver injury. In: Int. Symp. on Hepatotoxicity (Ed. M. Eliakim), p. 7. New York: Academic Press 1974

    Google Scholar 

  • Reiner, O., Athanassoponlus, R., Hellner, K. H., Murray, R. E., Uehleke, H.: Bildung von Chloroform aus Tetrachlorkohlenstoff in Lebermikrosomen, Lipidperoxidation und Zerstörung von Cytochrom P450. Arch. Toxikol. 29, 219–233 (1972)

    Google Scholar 

  • Schatz, G., Halsbrunner, E., Tuppy, H.: Intermitochondriale Deoxyribonucleinsäure in Säugetierzellen. Mh. Chem. 95, 1135–1142 (1964)

    Google Scholar 

  • Schulze, H. U., Staudinger, H.: Änderungen im Gehalt der Phospholipide von Lebermikrosomen unterschiedlich vorbehandelter Ratten und Meerschweinchen. Hoppe-Seylers Z. physiol. Chem. 351, 184–193 (1970)

    Google Scholar 

  • Schurig, R., Oberdisse, E.: The influence of rare-earths on hepatic gluconeogenesis. Naunyn-Schmiedebergs Arch. Pharmacol. 275, 419–433 (1972)

    Google Scholar 

  • Skipski, V. P., Peterson, R. F., Barclay, M.: Quantitative analysis of phospholipids by thinlayer chromatography. Biochem. J. 90, 374–378 (1964)

    Google Scholar 

  • Snyder, F., Cress, E. A., Kyker, G. C.: Liver lipid response to intravenous injection of rareearth in rats. J. Lipid Res. 1, 125–131 (1959)

    Google Scholar 

  • Snyder, F., Stephens, N.: Plasma free fatty acids and the rare earth fatty liver. Proc. Soc. exp. Biol. (N.Y.) 106, 202–204 (1961)

    Google Scholar 

  • Spiro, M. J., McKibbin, J. M.: The lipids of rat liver cell fractions. J. biol. Chem. 219, 643–651 (1956)

    Google Scholar 

  • Strobel, H. W., Lu, A. Y. H., Heidema, J., Coon, M. J.: Phosphatidyl requirement in the enzymatic reduction of hemoprotein P-450 and in fatty acid, hydrocarbon and drug hydroxylation. J. biol. Chem. 245, 4851–8454 (1970)

    Google Scholar 

  • Widnell, C. C., Tata, J. R.: A procedure for the isolation of enzymically active rat liver nuclei. Biochem. J. 92, 313–319 (1964)

    Google Scholar 

  • Zilversmit, D. B., Davies, A. K.: Microdetermination of plasma phospholipids by trichloroacetic acid precipitation. J. Lab. clin. Med. 35, 155–165 (1950)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lehmann, B.v., Oberdisse, E., Grajewski, O. et al. Subcellular distribution of phospholipids during liver damage induced by rare earths. Arch. Toxicol. 34, 89–101 (1975). https://doi.org/10.1007/BF00353309

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00353309

Key words

Schlüsselwörter

Navigation