title: Echinococcus granulosus tegumental enzymes as in vitro markers of pharmacological damage: a biochemical and molecular approach.
abstract: Cystic echinococcosis is a chronic, complex, and neglected disease. Novel therapeutical tools are needed to optimize human treatment. A number of compounds have been investigated, either using in vitro cultured parasites and/or applying in vivo rodent models. Although some of these compounds showed promising activities in vitro, and to some extent also in the rodent models, they have not been translated into clinical applications. Membrane enzyme activities in culture supernatants of treated protoscoleces with calcium modulator drugs and anthelmintic drugs were measured and provided an indication of compound efficacy. This work describes for the first time the detection of alkaline phosphatase, gamma-glutamyl-transpeptidase and acetylcholinesterase activities in supernatants of in vitro treated Echinococcus granulosus protoscoleces. Marked differences on the enzymatic activities in supernatants from drug treated cultures were detected. We demonstrated that those genes that show the highest degree of conservation when compared to orthologs, are constitutively and highly expressed in protoscoleces and metacestodes. Due to high sensibility and the lack of activity in supernatants of intact protoscoleces, gamma-glutamyl-transpeptidase is proposed as the ideal viability marker during in vitro pharmacological studies against E. granulosus protoscoleces.
authors.affiliation: Laboratorio de Zoonosis Parasitarias, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata (UNMdP), Funes 3250, 7600 Mar del Plata, Argentina. acumino@gmail.com
authors.forename: Andrea C
authors.initials: AC
authors.lastname: Cumino
authors.forename: M Celeste
authors.initials: MC
authors.lastname: Nicolao
authors.forename: Julia A
authors.initials: JA
authors.lastname: Loos
authors.forename: Guillermo
authors.initials: G
authors.lastname: Denegri
authors.forename: M Celina
authors.initials: MC
authors.lastname: Elissondo
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D015415:Biomarkers; D002118:Calcium; D048209:Echinococcus granulosus / Q000201:enzymology* / Q000378:metabolism* / Q000648:ultrastructure; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D034582:Integumentary System; D008969:Molecular Sequence Data
chemical_list: D000871:Anthelmintics; D015415:Biomarkers; D002118:Calcium