Title
Quantitative screening for anticestode drugs based on changes in baseline enzyme secretion by taenia crassiceps
Date Issued
01 February 2013
Access level
open access
Resource Type
journal article
Author(s)
Madrid E.
Nash T.
Helminth Immunology Sectiona and Gastrointestinal Parasites Section
Publisher(s)
Elsevier Ltd
Abstract
Neurocysticercosis (NCC), an infection of the brain with the larval stage of the Taenia solium tapeworm, is responsible for an estimated one-third of adult-onset epilepsy cases in regions of the world where it is endemic. Currently, anthelmintic drugs used for treatment of NCC are only partially effective, and there is, therefore, a pressing need for new therapeutic agents. Discovery of new anthelmintics with activity against T. solium has been limited by the lack of suitable sensitive assays that allow highthroughput screening. Using an in vitro culture system with Taenia crassiceps metacestodes, we demonstrate that changes in secretion of parasite-associated alkaline phosphatase (AP) and phosphoglucose isomerase (PGI) can be used to detect and quantify anthelmintic effects of praziquantel (PZQ), a drug with activity against T. solium. We applied two enzyme release assays to screen for anti-T. crassiceps activity in nonconventional antiparasitic drugs and demonstrate that nitazoxanide and artesunate induced release of both AP and PGI in differing time- and dose-related patterns. Furthermore, imatinib, a tyrosine kinase inhibitor previously reported to have parasiticidal activity against Schistosoma mansoni, also induced release of both AP and PGI in a dose-dependent manner, similar in pattern to that observed with the other anthelmintics. We also evaluated release of ATP into cyst supernatants as an indicator of drug effects but did not see any differences between treated and untreated cysts. These data provide the basis for rapid and quantitative screening assays for testing for anthelmintic activity in candidate anticestode agents. Copyright © 2013, American Society for Microbiology. All Rights Reserved.
Start page
990
End page
995
Volume
57
Issue
2
Language
English
OCDE Knowledge area
Parasitología Farmacología, Farmacia
Scopus EID
2-s2.0-84872837481
PubMed ID
Source
Antimicrobial Agents and Chemotherapy
ISSN of the container
10986596
Sources of information: Directorio de Producción Científica Scopus