Hostname: page-component-586b7cd67f-rdxmf Total loading time: 0 Render date: 2024-11-28T07:04:05.450Z Has data issue: false hasContentIssue false
  • English
  • Français

Lysosomes and tegument pathology in the chemotherapy of schistosomiasis with 1,7 -bis(p-aminophenoxy)heptane(153C51)

Published online by Cambridge University Press:  06 April 2009

S. D. M. Watts ,
A. Orpin  and
C. MacCormick
S. D. M. Watts
Affiliation:
Parasitology Department, The Wellcome Research Laboratories, Beckenham, Kent BR3 3BS
A. Orpin
Affiliation:
Electron Microscopy Suite, The Wellcome Research Laboratories, Beckenham, Kent BR3 3BS
C. MacCormick
Affiliation:
Electron Microscopy Suite, The Wellcome Research Laboratories, Beckenham, Kent BR3 3BS
Get access Rights & Permissions [Opens in a new window]

Summary

One therapeutic oral dose (400 mg/kg) of 153C51 administered to infested mice caused pathological changes in the dorsal region of the tegument of male Schistosoma mansoni during the period 3–24 h after treatment. These changes occurred prior to the ‘hepatic shift’. At the ultrastructural level they consisted of a gradual accumulation in the tegument epidermis of numerous membranous inclusions with the characteristics of residual lysosomes and changes in the localization of acid phosphatase, a lysosomal enzyme. It seemed likely that these changes were due to inhibition or exhaustion of enzyme in the epidermis, followed by re-synthesis of enzyme in the cell bodies and its export to the epidermis. The elimination of hydrolytic activity from lysosomes in the epidermis would explain the accumulation of residual lysosomes. Drug- treated parasites retained their disguise of host red blood cell ghost antigens as shown by indirect fluorescent antibody-labelling and, therefore, it seemed unlikely that immunological factors could be important in producing the tegument pathology.

Type
Research Article
Information
Parasitology , Volume 78 , Issue 3 , June 1979 , pp. 287 - 294
Copyright
Copyright © Cambridge University Press 1979

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Abraham, R., Hendy, R. J. & Grasso, P. (1968). Formation of myeloid bodies in rat liver lysosomes after chloroquine administration. Experimental and Molecular Pathology 212–29.CrossRefGoogle ScholarPubMed
Allison, A. C. & Young, M. R. (1964). Uptake of dyes and drugs by living cells in culture. Life Sciences 3, 1407–14.CrossRefGoogle ScholarPubMed
Bowen, I. D. (1968). Electron-cytochemical localisation of acid phosphatase activity in the digestive caeca of the desert locust. Journal of the Royal Microscopical Society 88, 279–89.CrossRefGoogle ScholarPubMed
Bueding, E. (1962). Effects of benzylic diamines on Schistosoma mansoni. Biochemical Pharmacology 11, 17–28.CrossRefGoogle ScholarPubMed
Clegg, J. A., Smithers, S. R. & Terry, R. J. (1970). Host antigens associated with schistosomes: observations on their attachment and their nature. Parasitology 61, 87–94.CrossRefGoogle ScholarPubMed
De Duve, C. & Wattlaux, R. (1966). Functions of lysosomes. Annual Review of Physiology 28, 435–92.CrossRefGoogle ScholarPubMed
Ericsson, J. L. E. (1969). Mechanisms of cellular autophagy. In Lysosomes in Biology and Pathology, vol. 2 (ed. Dingle, J. T. and Fell, H. B.), pp. 345–94. Amsterdam and London: North-Holland Publishing Company.Google Scholar
Hockley, D. J. & McLaren, D. J. (1973). Schistosoma mansoni: changes in the outer membrane of the tegument during development from cercaria to adult worm. International Journal for Parasitology 3, 13–25.CrossRefGoogle ScholarPubMed
Hruban, Z., Slesers, A. & Hopkins, E. (1972). Drug-induced and naturally occurring myeloid bodies. Laboratory Investigation 27, 62–70.Google ScholarPubMed
Lüllmann, H. & Lüllmann-Rauch, R. (1977). Drug-induced lipidoses. In Drug Design and Adverse Reactions, Alfred Benzon Symposium X, Munksgaard pp. 29–40. New York and London: Academic Press.Google Scholar
Morris, G. P. (1970). The effects of 1,7-bis(p-aminophenoxy)heptane on the ultrastructure of adult Schistosoma mansoni. Journal of Parasitology 56, Section II, 241.Google Scholar
Morris, G. P. & Threadgold, L. T. (1968). Ultrastructure of the tegument of adult Schistosoma mansoni. Journal of Parasitology 54, 15–27.CrossRefGoogle ScholarPubMed
Nimmo-Smith, R. H. & Standen, O. D. (1963). Phosphomonoesterases of Schistosoma mansoni. Experimental Parasitology 13, 305–22.CrossRefGoogle ScholarPubMed
Oyeriende, J. P. O. (1976). The effects of 1,7-bis(p-aminophenoxy)heptane on adult Schistosoma mansoni in mice. Nigerian Medical Journal 6, 392–7.Google Scholar
Pease, D. C. (1964). Histological Techniques for Electron Microscopy, pp. 381. London: Academic Press.Google Scholar
Pitt, D. (1975). Lysosomes and Cell Function, pp. 165. London: Longman.Google Scholar
Raison, C. G. & Standen, O. D. (1955). The schistosomicidal activity of symmetrical diaminodiphenoxyalkanes. British Journal of Pharmacology and Chemotherapy 10, 191–9.CrossRefGoogle ScholarPubMed
Smith, J. M., Reynolds, E. S. & Von Lichtenberg, F. (1969). The integument of Schistosoma mansoni. American Journal of Tropical Medicine and Hygiene 18, 28–49.CrossRefGoogle ScholarPubMed
Smithers, S. R., Terry, R. J. & Hockley, D. J. (1969). Host antigens in schistosomiasis. Proceedings of the Royal Society London, B 171, 483–94.Google ScholarPubMed
Standen, O. D. (1962). Observations in mice on the schistosomicidal properties of 1,7- bis(p-aminophenoxy)heptane in vivo and in vivo/in vitro. Proceedings of the Ciba Foundation Symposium on Bilharziasis pp. 266–86.CrossRefGoogle Scholar
Warhurst, P. & Hockley, D. J. (1967). Mode of action of chloroquine on Plasmodium berghei and P. cynomolgi. Nature, London 214, 935–6.CrossRefGoogle ScholarPubMed
Watts, S. D. M. (1978). The effects of 1,7-bis(p-aminophenoxy)heptane (153C51) on glucose utilization by Schistosoma mansoni. Comparative Biochemistry and Physiology 60, 109–14.Google Scholar
Weissmann, G. (1969). The effects of steroids and drugs on lysosomes. In Lysosomes in Biology and Pathology, vol. 1 (ed. Dingle, J. T. and Fell, H. B.), pp. 276–95. Amsterdam and London: North-Holland Publishing Company.Google Scholar
Wheater, P. R. & Wilson, R. A. (1976). The tegument of schistosoma mansoni: a histochemical investigation. Parasitology 72, 99–109.CrossRefGoogle ScholarPubMed
Wilson, R. A. & Barnes, P. E. (1974). The tegument of Schistosoma mansoni: observations on the formation, structure and composition of cytoplasmic inclusions in relation to tegument function. Parasitology 68, 239–58.CrossRefGoogle ScholarPubMed