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In vitro effects of isoprinosine and a dipeptide methyl ester on Echinococcus multilocularis protoscoleces
P Lawton1, N Walchshofer, M E Sarciron
1Département de Parasitologie et Mycologie Médicale, Faculté de Pharmacie, Lyon, France. 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.
Insights
Isoprinosine, inosine, and L-Phe-Phe-OMe demonstrate direct anti-parasitic effects against Echinococcus multilocularis protoscoleces in vitro. These compounds show dose- and time-dependent activity, with L-Phe-Phe-OMe exhibiting potent effects comparable to praziquantel.
Area of Science:
- Parasitology
- Pharmacology
- Biochemistry
Background:
- Echinococcus multilocularis is a significant human pathogen.
- Understanding the direct effects of potential therapeutic agents on parasite stages is crucial for developing effective treatments.
- Isoprinosine and its active component inosine have shown promise in previous in vivo studies.
Purpose of the Study:
- To evaluate the in vitro activity of isoprinosine, inosine, and L-Phe-Phe-OMe against isolated Echinococcus multilocularis protoscoleces.
- To assess the dose- and time-dependent effects of these compounds.
- To compare their activity and ultrastructural impact with praziquantel.
Main Methods:
- In vitro maintenance of Echinococcus multilocularis protoscoleces/vesicles.
- Viability assessment using eosin exclusion.
- Quantitative and qualitative activity evaluation over 24 and 48 hours.
- Ultrastructural analysis of parasite tissues.
Main Results:
- Isoprinosine and inosine exhibited dose- and time-dependent activity, with inosine acting more rapidly.
- L-Phe-Phe-OMe demonstrated high activity, comparable to praziquantel.
- Ultrastructural damage was more pronounced with L-Phe-Phe-OMe, similar to praziquantel.
- Inosine and isoprinosine's activity appeared to target parasite metabolism, with delayed ultrastructural changes.
Conclusions:
- The in vivo efficacy of isoprinosine and inosine against Echinococcus multilocularis is largely due to their direct action on the parasite.
- L-Phe-Phe-OMe also exerts a direct parasiticidal effect, with a mechanism of action similar to praziquantel.
- These findings support the direct anti-parasitic role of these compounds and inform future therapeutic strategies.