In vitro metacestodicidal activities of genistein and other isoflavones against Echinococcus multilocularis and Echinococcus granulosus

Naguleswaran, Arunasalam; Spicher, Martin; Vonlaufen, Nathalie; Ortega-Mora, Luis M; Torgerson, Paul; Gottstein, Bruno; Hemphill, Andrew (2006). In vitro metacestodicidal activities of genistein and other isoflavones against Echinococcus multilocularis and Echinococcus granulosus. Antimicrobial agents and chemotherapy, 50(11), pp. 3770-8. Washington, D.C.: American Society for Microbiology 10.1128/AAC.00578-06

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Echinococcus multilocularis and Echinococcus granulosus metacestode infections in humans cause alveolar echinococcosis and cystic echinococcosis, respectively, in which metacestode development in visceral organs often results in particular organ failure. Further, cystic hydatidosis in farm animals causes severe economic losses. Although benzimidazole derivatives such as mebendazole and albendazole are being used as therapeutic agents, there is often no complete recovery after treatment. Hence, in searching for novel treatment options, we examined the in vitro efficacies of a number of isoflavones against Echinococcus metacestodes and protoscoleces. The most prominent isoflavone, genistein, exhibits significant metacestodicidal activity in vitro. However, genistein binds to the estrogen receptor and can thus induce estrogenic effects, which is a major concern during long-term chemotherapy. We have therefore investigated the activities of a number of synthetic genistein derivatives carrying a modified estrogen receptor binding site. One of these, Rm6423, induced dramatic breakdown of the structural integrity of the metacestode germinal layer of both species within 5 to 7 days of in vitro treatment. Further, examination of the culture medium revealed increased leakage of parasite proteins into the medium during treatment, but zymography demonstrated a decrease in the activity of metalloproteases. Moreover, two of the genistein derivatives, Rm6423 and Rm6426, induced considerable damage in E. granulosus protoscoleces, rendering them nonviable. These findings demonstrate that synthetic isoflavones exhibit distinct in vitro effects on Echinococcus metacestodes and protoscoleces, which could potentially be exploited further for the development of novel chemotherapeutical tools against larval-stage Echinococcus infection.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Parasitology

UniBE Contributor:

Naguleswaran, Arunasalam; Spicher, Martin; Vonlaufen, Nathalie Françoise F.; Gottstein, Bruno and Hemphill, Andrew

ISSN:

0066-4804

Publisher:

American Society for Microbiology

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:45

Last Modified:

04 May 2014 23:13

Publisher DOI:

10.1128/AAC.00578-06

PubMed ID:

16954323

Web of Science ID:

000241935200033

URI:

https://boris.unibe.ch/id/eprint/18668 (FactScience: 875)

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