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In vitro effects of isoprinosine and a dipeptide methyl ester on Echinococcus multilocularis protoscoleces

Published online by Cambridge University Press:  12 April 2024

P. Lawton*
Affiliation:
Département de Parasitologie et Mycologie Médicale
N. Walchshofer
Affiliation:
Laboratoire de Chimie Organique, Faculté de Pharmacie, 8 avenue Rockefeller, F-69373 Lyon Cedex 08, France
M.E. Sarciron
Affiliation:
Département de Parasitologie et Mycologie Médicale
*
*Fax: +33 4 78 77 71 58 E-mail: lawton@univ-lyon1.fr

Abstract

A protoscoleces/vesicles in vitro maintenance test with assessment of viability by eosin exclusion was used to evaluate the quantitative and qualitative activities of isoprinosine, its active component inosine and the dipeptide methylester L-Phe-Phe-OMe on isolated protoscoleces of Echinococcus multilocularis for 24 and 48 h. Isoprinosine and inosine showed dose- and time-dependent activity, the latter displaying a more rapid effect than the former. A high activity was shown with L-Phe-Phe-OMe, when compared to praziquantel. Ultrastructural alterations were much more striking with L-Phe-Phe-OMe, with an effect similar to that of praziquantel, whereas the chemotherapeutic activity of inosine and isoprinosine appeared to be directed against a metabolic target, with a lethal effect not immediately visible at the ultrastructural level. Thus, the previously reported in vivo activities of these drugs result largely from a direct effect on the parasite.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2001

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References

Casado, N. & Rodríguez-Caabeiro, F. (1989) Ultrastructural study of in vitro larval development of Echinococcus granulosus protoscoleces. International Journal for Parasitology 19, 2128.CrossRefGoogle ScholarPubMed
Casado, N., Perez-Serrano, J., Denegri, G. & Rodriguez-Caabeiro, F. (1994) Development of truncated microtriches in Echinococcus granulosus protoscolices. Parasitology Research 80, 355357.CrossRefGoogle ScholarPubMed
Casado, N., Pérez-Serrano, J., Denegri, G. & Rodríguez-Caabeiro, F. (1996) Development of a chemotherapeutic model for the in vitro screening of drugs against Echinococcus granulosus cysts: the effects of an albendazole-albendazole sulphoxide combination. International Journal for Parasitology 26, 5965.CrossRefGoogle ScholarPubMed
Delabre-Defayolle, I., Sarciron, M.E., Audin, P., Gabrion, C., Duriez, T., Paris, J. & Petavy, A.F. (1989) Echinococcus multilocularis metacestodes: biochemical and ultrastructural investigations on the effect of isatin (2,3-indoline dione) in vivo . Journal of Antimicrobial Chemotherapy 23, 237245.CrossRefGoogle Scholar
Eckert, J. & Amman, R.W. (1995) Clinical diagnosis and treatment of echinococcosis in humans. 411463 in Thompson, R.C.A. & Lymbery, A.J. (Eds) Echinococcus and hydatid disease Wallingford, CAB International.Google Scholar
Emery, I., Bories, C., Liance, M. & Houin, R. (1995) In vitro quantitative assessment of Echinococcus multilocularis metacestode viability after in vivo and in vitro maintenance. International Journal for Parasitology 25, 275278.CrossRefGoogle ScholarPubMed
Gabrion, C., Walbaum, S. & Petavy, A.F. (1995) Echinococcus multilocularis protoscoleces and hepatic cell activity in vitro . International Journal for Parasitology 25, 127130.CrossRefGoogle ScholarPubMed
Garcia-Llamazares, J.L., Alvarez-de-Felipe, A.I., Redondo-Cardena, P.A. & Prieto-Fernandez, J.G. (1998) Echinococcus granulosus: membrane permeability of secondary hydatid cysts to albendazole sulfoxide. Parasitology Research 84, 417420.CrossRefGoogle ScholarPubMed
Hemphill, A. & Gottstein, B. (1995) Immunology and morphology studies on the proliferation of in vitro cultivated Echinococcus multilocularis metacestodes. Parasitology Research 81, 605614.CrossRefGoogle ScholarPubMed
Jura, H., Bader, A., Hartmann, M., Maschek, H. & Frosch, M. (1996) Hepatic tissue culture model for study of host-parasite interactions in alveolar echinococcosis. Infection and Immunity 64, 34843490.CrossRefGoogle ScholarPubMed
Lorenzini, R. & Ruggieri, A. (1990) An experimental in vitro model for evaluating drugs against protoscoleces of Echinococcus granulosus . Journal of Helminthology 64, 343348.CrossRefGoogle ScholarPubMed
Marchiondo, A.A., Ming, R., Andersen, F.L., Slusser, J.H. & Conder, G.A. (1994) Enhanced larval cyst growth of Echinococcus multilocularis in praziquantel-treated jirds (Meriones unguiculatus). American Journal of Tropical Medicine and Hygiene 50, 2027.CrossRefGoogle ScholarPubMed
Martin, R.J., Robertson, A.P. & Bjorn, H. (1997) Target sites of anthelminthics. Parasitology 114, S111S124.CrossRefGoogle Scholar
Morris, D.L., Taylor, D., Daniels, D. & Richards, K.S. (1987) Determination of minimum effective concentration of praziquantel in in vitro cultures of protoscoleces of Echinococcus granulosus . Transactions of the Royal Society of Tropical Medicine and Hygiene 81, 494497.CrossRefGoogle ScholarPubMed
Richards, K.S., Morris, D.L., Daniels, D. & Riley, E.M. (1988) Echinococcus granulosus: the effects of praziquantel in vivo and in vitro, on the ultrastructure of equine strain murine cysts. Parasitology 96, 323336.CrossRefGoogle ScholarPubMed
Sarciron, M.E., Al-Nahhas, S., Walbaum, S., Raynaud, G. & Petavy, A.F. (1991) Treatment of experimental alveolar echinococcosis: comparative study of mebendazole, Isoprinosine and a mebendazole-Isoprinosine association. Tropical Medicine and Parasitology 42, 417419.Google Scholar
Sarciron, M.E., Delabre, I., Walbaum, S., Raynaud, G. & Petavy, A.F. (1992) Effects of multiple doses of Isoprinosine on Echinococcus multilocularis metacestodes. Antimicrobial Agents and Chemotherapy 36, 191194.CrossRefGoogle ScholarPubMed
Sarciron, M.E., Walbaum, S., Arsac, C., Raynaud, G. & Petavy, A.F. (1993) Echinococcus granulosus: Isoprinosine treatment of the metacestode stage. American Journal of Tropical Medicine and Hygiene 48, 658665.CrossRefGoogle ScholarPubMed
Sarciron, M.E., Walbaum, S. & Petavy, A.F. (1995) Effects of Isoprinosine on Echinococcus multilocularis and E. granulosus metacestodes. Parasitology Research 81, 329333.CrossRefGoogle ScholarPubMed
Sarciron, M.E., Walchshofer, N., Walbaum, S., Arsac, C., Descotes, J., Petavy, A.F. & Paris, J. (1997) Increases in the effects of albendazole on Echinococcus multilocularis metacestodes by the dipeptide methyl ester (Phe-Phe-OMe). American Journal of Tropical Medicine and Hygiene 56, 226230.CrossRefGoogle ScholarPubMed
Sarciron, M.E., Lawton, P., Saccharin, C., Petavy, A.F. & Peyron, F. (1997) Effects of 2′, 3′-dideoxyinosine on Toxoplasma gondii cysts in mice. Antimicrobial Agents and Chemotherapy 41, 15311536.CrossRefGoogle ScholarPubMed
Sarciron, M.E., Lawton, P., Petavy, A.F. & Peyron, F. (1998) Alterations of Toxoplasma gondii induced by 2′,3′-dideoxyinosine in vitro . Journal of Parasitology 84, 10551059.CrossRefGoogle ScholarPubMed
Suchail, S., Sarciron, M.E. & Petavy, A.F. (1998) Purine metabolism in Echinococcus multilocularis . Comparative Biochemistry and Physiology 120, 633637.CrossRefGoogle ScholarPubMed
Taylor, D.H., Morris, D.L. & Richards, K.S. (1989) Echinococcus granulosus: in vitro maintenance of whole cysts and the assessment of the effects of albendazole sulphoxide and praziquantel on the germinal layer. Transactions of the Royal Society of Tropical Medicine and Hygiene 83, 535538.CrossRefGoogle ScholarPubMed
Walchshofer, N., Sarciron, M.E., Arsac, C., Walbaum, S., Paris, J. & Petavy, A.F. (1993) Biological effects of a dipeptide methyl ester on Echinococcus multilocularis metacestodes in vivo . International Journal of Pharmaceutics 100, 271277.CrossRefGoogle Scholar
Walchshofer, N., Sarciron, M.E., Garnier, F., Delatour, P., Petavy, A.F. & Paris, J. (1997) Anthelmintic activity of 3,6-dibenzyl-2,5-dioxopiperazine, cyclo (L-Phe-L-Phe). Aminoacids 12, 4147.Google Scholar