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Effect of cyclosporin A on the survival and ultrastructure of Echinococcus granulosus protoscoleces in vitro

Published online by Cambridge University Press:  14 September 2004

A. L. COLEBROOK ,
D. J. JENKINS ,
M. K. JONES ,
L. TATARCZUCH  and
M. W. LIGHTOWLERS
A. L. COLEBROOK
Affiliation:
Department of Veterinary Science, University of Melbourne, 250 Princes Highway, Werribee, 3030 Victoria, Australia
D. J. JENKINS
Affiliation:
Department of Veterinary Science, University of Melbourne, 250 Princes Highway, Werribee, 3030 Victoria, Australia
M. K. JONES
Affiliation:
Department of Veterinary Science, University of Melbourne, 250 Princes Highway, Werribee, 3030 Victoria, Australia
L. TATARCZUCH
Affiliation:
Department of Veterinary Science, University of Melbourne, 250 Princes Highway, Werribee, 3030 Victoria, Australia
M. W. LIGHTOWLERS
Affiliation:
Department of Veterinary Science, University of Melbourne, 250 Princes Highway, Werribee, 3030 Victoria, Australia
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Abstract

Surgical treatment of human hydatidsosis involves the use of various scolicidal agents to kill infective Echinococcus granulosus protoscoleces that may disseminate into the peritoneal cavity during surgery and potentially re-infect the patient. Currently, no scolicidal agent is completely effective in killing intracystic protoscoleces in humans. Cyclosporin A (CsA) has previously been found to be lethal for E. granulosus protoscoleces in vitro. In this study, we further assessed the effectiveness of CsA as a scolicidal agent by testing the toxic effect of CsA at higher doses over various time-periods. Experiments were performed on activated and unactivated protoscoleces cultured in nutrient medium or sheep hydatid cyst fluid. All activated protoscoleces were killed following culture in 100 μg/ml of CsA for 3 days and 50 or 20 μg/ml for 5 days. The lethal effect of CsA on unactivated protoscoleces varied but reached 100% over 15 days in culture with 100 or 50 μg/ml of CsA. Pulse treatment of protoscoleces with 50, 20 or 10 μg/ml of CsA for 5 min or 72 h killed all parasites by day 10 and day 5 respectively. Untreated protoscoleces remained greater than 95% viable for the duration of experiments. Changes in protoscolex ultrastructure induced by treatment with 10 μg/ml of CsA over 10 days in in vitro culture was assessed by TEM. Protoscolex alterations observed in treated parasites included an increase in cellular vacuolization, swelling of mitochondria, rounding of cells, damage to the tegument, decrease in glycogen, a breakdown of the extracellular matrix and an increase in lipid globules. The untreated protoscoleces, by comparison, had few changes during the 10-day culture period with the exception of large amounts of extracellular glycogen observed in the protoscoleces at culture days 7 and 10. From these results, CsA is clearly an effective scolicidal agent in vitro that may have potential application as a new therapeutic agent in the treatment of human hydatid disease.

Keywords

Echinococcus granulosushydatidcyclosporin Ascolicidal agent
Type
Research Article
Information
Parasitology , Volume 129 , Issue 4 , October 2004 , pp. 497 - 504
Copyright
2004 Cambridge University Press

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References

REFERENCES

BOREL, J. F., BAUMANN, G., CHAPMAN, I., DONATSCH, P., FAHR, A., MUELLER, E. A. & VIGOURET, J. M. (1996). In vivo pharmacological effects of ciclosporin and some analogues. Advances in Pharmacology 35, 115–246.CrossRefGoogle Scholar
CASADO, N., RODRIGUEZ-CAABEIRO, F., JIMENEZ, A., CRIADO, A. & DE ARMAS, C. (1989). In vitro effects of levamisole and ivermectin against Echinococcus granulosus protoscoleces. International Journal for Parasitology 19, 945–947.CrossRefGoogle Scholar
CHAPPELL, L. H. & WASTLING, J. M. (1992). Cyclosporin A: antiparasite drug, modulator of the host–parasite relationship and immunosuppressant. Parasitology 105 (Suppl.), S25–S40.CrossRefGoogle Scholar
COLEBROOK, A., JENKINS, D. & LIGHTOWLERS, M. (2002). Anti-parasitic effect of cyclosporin A on Echinococcus granulosus and characterization of the associated cyclophilin protein. Parasitology 125, 485–493.CrossRefGoogle Scholar
DEGER, E., HOKELEK, M., DEGER, B. A., TUTAR, E., ASIL, M. & PAKDEMIRLI, E. (2000). A new therapeutic approach for the treatment of cystic echinococcosis: percutaneous albendazole sulphoxide injection without reaspiration. American Journal of Gastroenterology 95, 248–254.CrossRefGoogle Scholar
FILICE, C., BRUNETTI, E., D'ANDREA, F. & FILICE, G. (1997). Minimal invasive treatment for hydatid abdominal cysts: PAIR (Puncture, Aspiration, Injection, Reaspiration) – state of the art. World Health Organization, Geneva WHO/CTD/SIP/97.3, 1–41.Google Scholar
FOURNIER, N., DUCET, G. & CREVAT, A. (1987). Action of cyclosporine on mitochondrial calcium fluxes. Journal of Bioenergy and Biomembranes 19, 297–303.CrossRefGoogle Scholar
HOKELEK, M., DEGER, B. A., DEGER, E., TUTAR, E. & SUNBUL, M. (2002). Ivermectin used in percutaneous drug injection method for the treatment of liver hydatid disease in sheep. Gastroenterology 122, 957–962.CrossRefGoogle Scholar
HURD, H., MACKENZIE, K. S. & CHAPPELL, L. H. (1993). Anthelmintic effects of cyclosporin A on protoscoleces and secondary hydatid cysts of Echinococcus granulosus in the mouse. International Journal for Parasitology 23, 315–320.CrossRefGoogle Scholar
JURADO, F., BELLON, J. M., PAREJA, J. A., GOLITSIN, A., MILLAN, L., PASCUAL, G. & BUJAN, J. (1998). Effects of ischaemia-reperfusion and cyclosporin-A on cardiac muscle ultrastructure. Histology and Histopathology 13, 761–774.Google Scholar
KHATTAB, A., PICA-MATTOCCIA, L., KLINKERT, M. Q., WENGER, R. & CIOLI, D. (1998). Cyclosporins: lack of correlation between antischistosomal properties and inhibition of cyclophilin isomerase activity. Experimental Parasitology 90, 103–109.CrossRefGoogle Scholar
LIANCE, M., BRESSON-HADNI, S., VUITTON, D. A., LENYS, D., CARBILLET, J. P. & HOUIN, R. (1992). Effects of cyclosporin A on the course of murine alveolar Echinococcosis and on specific cellular and humoral immune responses against Echinococcus multilocularis. International Journal for Parasitology 22, 23–28.CrossRefGoogle Scholar
McLAUCHLAN, P. E., ROBERTS, H. C. & CHAPPELL, L. H. (2000). Mode of action of cyclosporin A against Hymenolepis microstoma (Cestoda): relationship between cyclophilin binding and drug-induced damage. Parasitology 121, 661–670.CrossRefGoogle Scholar
McMANUS, D. P. & SMYTH, J. D. (1982). Intermediary carbohydrate metabolism in protoscoleces of Echinococcus granulosus (horse and sheep strains) and E. multilocularis. Parasitology 84, 351–366.CrossRefGoogle Scholar
MUNRO, G. H. & McLAREN, D. J. (1990). Toxicity of cyclosporin A (CsA) against developmental stages of Schistosoma mansoni in mice. Parasitology 100, 29–34.CrossRefGoogle Scholar
OCHIENG-MITULA, P. J. & BURT, M. D. (1996). The effects of ivermectin on the hydatid cyst of Echinococcus granulosus after direct injection at laparotomy. Journal of Parasitology 82, 155–157.CrossRefGoogle Scholar
PAGE, A. P., KUMAR, S. & CARLOW, C. K. S. (1995). Parasite cyclophilins and antiparasite activity of cyclosporin A. Parasitology Today 11, 385–389.CrossRefGoogle Scholar
PONS, H. A., ADAMS, S. & STADECKER, M. J. (1988). Schistosoma mansoni: the basis for the antischistosomal effect of cyclosporine A. Experimental Parasitology 67, 190–198.CrossRefGoogle Scholar
RICKARD, M. D. & BELL, K. J. (1971). Successful vaccination of lambs against infection with Taenia ovis using antigens produced during in vitro cultivation of the larval stages. Research in Veterinary Science 12, 401–402.Google Scholar
RODRIGUEZ-CONTRERAS, D., SKELLY, P. J., LANDA, A., SHOEMAKER, C. B. & LACLETTE, J. P. (1998). Molecular and functional characterization and tissue localization of 2 glucose transporter homologues (TGTP1 and TGTP2) from the tapeworm, Taenia solium. Parasitology 117, 579–588.CrossRefGoogle Scholar
VADAS, M. A., DAVID, J. R., BUTTERWORTH, A., PISANI, N. T. & SIONGOK, T. A. (1979). A new method for the purification of human eosinophils and neutrophils, and a comparison of the ability of these cells to damage schistosomula of Schistosoma mansoni. Journal of Immunology 122, 1228–1236.Google Scholar
VON GRAFFENRIED, B. (1989). Sandimmun (ciclosporin) in autoimmune diseases. Overview on early clinical experience (status September 1987). American Journal of Nephrology 9 (Suppl. 1), 51–56.CrossRefGoogle Scholar
WASTLING, J. M. & CHAPPELL, L. H. (1994). Cyclosporin A: drug treatment in vivo affects the kinetics of [14C] glucose transport in Hymenolepis microstoma in vitro. Parasitology 108, 223–228.CrossRefGoogle Scholar
WORLD HEALTH ORGANIZATION (1996). Guidelines for the treatment of cystic and alveolar echinococcosis in humans. Bulletin of the World Health Organization 74, 231–242.