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Zur Enzyminduktion in der Leber nach oraler Lindanapplikation

Funktionelle und morphologische Untersuchungen an Ratten

Enzyme induction in the liver following administration of Lindane by the oral route

A functional and morphological study in rats

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Abstract

Following short-term oral administration of Lindane (5 mg/kg, 20 mg/ kg) to male rats, various functional, biochemical, histochemical and electronmicroscope investigations were performed. No effects of the Lindane medication were found in movement and exploration (open-field test), liver weight, and the histochemically presented enzymes. A dose-dependent and time-dependent reduction in the duration of sleep was measured after i.p. pentobarbital. There were no differences in the liver glycogen levels of treated and control animals when food was available to the animals ad libitum. After food had been withdrawn for 24 h, a tendency to reduced liver glycogen was observed in the treated animals. The excretion of ascorbic acid in the urine was several times higher than normal, while the ascorbic acid concentration in blood serum was doubled (attributed to transport effect). The electron microscope revealed a distinct increase in the smooth endoplasmic reticulum, particularly in hepatocytes of the intermediary zone.

The observed increase in free ribosomes was thought to be connected with the intensified formation of microsomal protein. The reduced glycogen of individual cells, also observed with the electron microscope, was explained as a result of the change in metabolism caused by enzyme induction (increase in formation of glucuronic acid, increased ascorbic acid synthesis).

In all, no hepatotoxic effects of the test substance were found with the given experimental procedure, so the functional and morphological equivalents of enzyme induction can be interpreted as adaptive changes.

Zusammenfassung

Nach kurzzeitiger oraler Lindanapplikation (5 mg/kg, 20 mg/kg) wurden an männlichen Ratten verschiedene funktionelle, biochemische, histochemische und elektronenmikroskopische Untersuchungen angestellt. Dabei wurde keine Beeinflussung der Motilität und Exploration (open field-Test), der Lebergewichte und der histochemisch dargestellten Enzyme durch die Lindanmedikation gefunden. Die Schlafzeit, gemessen nach Pentobarbital i.p., war dosisund zeitabhängig reduziert. Der Leberglykogengehalt von behandelten und Kontrolltieren unterschied sich nicht, wenn die Tiere Futter ad libitum aufnehmen konnten. Nach 24 Std Futterentzug wurde bei den behandelten Tieren eine Tendenz zur Glykogenverminderung in der Leber festgestellt. Die Ascorbinsäureausscheidung im Urin war um ein Vielfaches erhöht, während das Blutserum eine Verdoppelung der Ascorbinsäurekonzentration aufwies (als Transporteffekt gedeutet). Elektronenmikroskopisch fand sich eine deutliche Vermehrung des glatten, endoplasmatischen Reticulum, besonders in Hepatocyten der Intermediärzone.

Die gefundene Zunahme freier Ribosomen wird mit der verstärkten Bildung von mikrosomalem Protein in Verbindung gebracht. Die auch elektronenoptisch dargestellte Glykogenverminderung einzelner Zellen läßt sich als Folge des unter der Enzyminduktion veränderten Metabolismus (erhöhte Glucuronsäurebildung, verstärkte Ascorbinsäuresynthese) erklären.

Insgesamt konnte mit der gegebenen Versuchsanstellung kein Hinweis auf hepatotoxische Wirkungen der Prüfsubstanz gefunden werden, so daß sich die funktionellen und morphologischen Äquivalente der Enzyminduktion als adaptative Veränderungen interpretieren lassen.

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Authors and Affiliations

  1. Abteilung für Experimentelle Pathologie und Toxikologie, C. H. Boehringer Sohn, 6507, Ingelheim

    M. Herbst, J. Guénard, H. Köllmer & H. Stötzer

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  1. M. Herbst
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  2. J. Guénard
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  3. H. Köllmer
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  4. H. Stötzer
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Auszugsweise als Vortrag gehalten anläßlich der 22. Tagung der Europäischen Arbeitsgemeinschaft für Veterinärpathologen am 12. Juni 1973 in Karlsruhe.

Für sorgfältige technische Mitarbeit bedanken wir uns bei Frau H. Rixner, Frau M. Bolender, Frau J. Lempik, Frl. E. Nieraad, Herrn Th. Biefel, Herrn P. Fischer und Herrn D. Wallenstein.

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Herbst, M., Guénard, J., Köllmer, H. et al. Zur Enzyminduktion in der Leber nach oraler Lindanapplikation. Arch. Toxicol. 32, 115–130 (1974). https://doi.org/10.1007/BF00316232

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  • DOI: https://doi.org/10.1007/BF00316232

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