European Journal of Clinical Pharmacology

, Volume 19, Issue 6, pp 417–421 | Cite as

Effects of pexid on liver cell cultures ultrastructural and histoenzymological studies

  • A. Lageron
  • J. Scotto
  • M. Gautier
Originals

Summary

The effects of different doses of Pexid on cultured liver cells have been studied by ultrastructural and histoenzymological techniques. Two types of abnormal lysosomal inclusions were seen: clear matrix inclusions with either homogeneous or tiny lamellar structures, and dark matrix inclusions with clear vacuoles and either random or myelin-like lamellar structures. These patterns correspond to storage of triglycerides, phospholipids and gangliosides, either singly or together.

Key words

pexid liver cells cellular abnormal inclusion lipid storage lysosomal storage disorder 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Beaugrand M, Poupon R, Levy VG, Callard P, Lageron A, Lecomte D, Darnis F, Ferrier JP (1978) Lésions hépatiques dues au maléate de perhexiline. Etude clinique, biologique, histopathologique, ultranstructurale et biochimique de 7 cas. Gastroenterol Clin Biol 2: 579–588Google Scholar
  2. 2.
    Brinkley PR, Murphy P, Richardson LC (1967) Procedure for embedding in situ selected cells cultured in vitro. J Cell Biol 35: 279–283Google Scholar
  3. 3.
    de la Iglesia FA, Feuer G, Takada A, Matsuda Y (1974) Morphologic studies on secondary phospholipidosis in human liver. Lab Invest 30: 539–549Google Scholar
  4. 4.
    Hauw JJ, Boutry JM, Hamam S, Escourolle R (1978) Lipidose médicamenteuse induite en culture de ganglion spinal de souris par le maléate de perhexiline. Résultats préliminaires concernant la toxicité aiguë du médicament. CR Acad Sci Paris D 287: 959–961Google Scholar
  5. 5.
    Hauw JJ, Singer B, Poupon R, Lecomte D, de Saint-Maur PP, Lageron A, Pollet S (1978) Inclusions polymorphes diffuses chez un malade traité par le maléate de perhexiline. Nouv Presse Méd 7: 817–820Google Scholar
  6. 6.
    Hruban Z, Slesers A, Hopkins E (1972) Drug-induced and naturally occuring myeloid bodies. Lab Invest 27: 62–70Google Scholar
  7. 7.
    Jung JH, Suzuki K (1978) Morphological changes in CNS of rats treated with perhexiline maleate (Pexid). Acta Neuropathol 42: 159–164Google Scholar
  8. 8.
    Lageron A (1977) Lipidic liver changes induced by perhexiline maleate. Sixth Intern. Symposium on drugs affecting lipid metabolism, PhiladelphiaGoogle Scholar
  9. 9.
    Lageron A (1979) Modifications histoenzymologiques induites par le maléate de perhexiline au niveau du foie humain. Med Chir Dig 8: 415–417Google Scholar
  10. 10.
    Lageron A, Levy VG, Lecomte D, de Saint-Maur PP (1977) Surcharge hépatique en gangliosides après maléate de perhexiline. Evolution morphologique et biochimique. Nouv Presse Méd 6: 2859–2864Google Scholar
  11. 11.
    Lageron A, Poupon R, de Saint-Maur PP, Levy VG (1977) Liver ganglioside storage after perhexiline maleate. Lancet 1: 483Google Scholar
  12. 12.
    Le Guilly Y, Lenir P, Bourel M, Poupon R, Guillouzo A (1970) La culture prolongée du tissu hépatique humain adulte. Pathol Biol 18: 733–741Google Scholar
  13. 13.
    Lemonnier F, Gautier M, Moati N, Lemonnier A (1976) Comparative study of extracellular aminoacids in culture of human liver and fibroblastic cells. In Vitro 12: 460–466Google Scholar
  14. 14.
    Lüllmann H, Lüllmann-Rauch R (1978) Perhexiline Induces Generalized Lipidosis in Rats. Klin Wochenschr 56: 309–310Google Scholar
  15. 15.
    Lüllmann H, Lüllmann-Rauch R, Wassermann O (1975) Drug-induced phospholipidoses. CRC Crit Rev Toxicol 4: 185–218Google Scholar
  16. 16.
    Mikol J (1979) Lésions nerveuses et musculaires induites par le maléate de perhexiline: Association à une microangiopathie de type diabétique. Arch Anat Cytol Pathol 27: 175–181Google Scholar
  17. 17.
    Paliard P, Vitrey D, Fournier G, Belhadjali J, Patricot L, Berger F (1978) Perhexiline maleate-induced hepatitis. Digestion 17: 419–427Google Scholar
  18. 18.
    Pearse AGE (1968) Histochemistry. Theoretical and applied. 2 vol, 3rd edit. Churchill, LondonGoogle Scholar
  19. 19.
    Pessayre D, Bichara M, Feldmann G, Degott Cl, Potet F, Benhamou JP (1979) Perhexiline maleate-induced cirrhosis. Gastroenterology 76: 170–177Google Scholar
  20. 20.
    Picard R, Tixier-Vidal A (1974) Description d'une méthode permettant la sélection et l'étude ultrastructurale de plages cellulaires dans des monocouches hétérogènes cultivées en flacon de plastique. J Microsc 20: 80aGoogle Scholar
  21. 21.
    Pollet S, Hauw JJ, Turpin JC, Le Saux F, Escourolle R, Baumann N (1979) Analysis of the major lipid classes in human peripheral nerve biopsies. J Neurol Sci 41: 199–206Google Scholar
  22. 22.
    Singlas E, Goujet MA, Simon P (1978) Pharmacokinetics of perhexiline maleate in anginal patients with and without peripheral neuropathy. Eur. J Clin Pharmacol 14: 195–201Google Scholar
  23. 23.
    Yamamoto A, Adachi S, Matsuzawa Y, Kitani T, Hiraoka A, Seki KI (1976) Studies on drug-induced lipidosis: VII. Effects of Bis-β-diethylaminoethylether of Hexestrol, Chloroquine, Homochlorocyclizine, Prenylamine, and Diazacholesterol on the lipid Composition of rat liver and Kidney. Lipids 11: 616–622Google Scholar

Copyright information

© Springer-Verlag 1981

Authors and Affiliations

  • A. Lageron
    • 1
  • J. Scotto
    • 2
  • M. Gautier
    • 2
  1. 1.INSERM U9 184ParisFrance
  2. 2.INSERM U56, Unité de recherches d'hépatologie infantileHôpital BicêtreParisFrance

Personalised recommendations