Validation of sensitivity to praziquantel using Schistosoma mansoni worm muscle tension and Ca2+-uptake as possible in vitro correlates to in vivo ED50 determination

International Journal for Parasitology
S William, Sanaa Botros

Abstract

Schistosome worm muscle tension and [45Ca2+]-uptake were tested as possible correlates of susceptibility to praziquantel (PZQ) assessed by estimating the drug ED50. Schistosoma mansoni cercariae of PZQ sensitive (S-CD, S-MOC and S-GP) and insensitive S. mansoni isolates (I-EE2, I-BANL and I-Senegal 47) were used to infect batches of CD-1 Swiss albino mice. Seven weeks after infection, animals of each batch were divided into six groups. Five of them received PZQ in doses of 12.5, 25, 50, 100 or 200 mg/kg PZQ, respectively, for five consecutive days, while the sixth was left as untreated controls. Two weeks after treatment mice were sacrificed, perfused and PZQ ED50's were estimated. Male worms recovered from infected untreated controls were examined for their muscle tension increase in response to PZQ using a physiological recorder coupled to a photooptic transducer. [45Ca2+]-uptake of male worms in the presence and absence of PZQ was determined using a liquid scintillation beta counter. Data revealed that PZQ insensitive isolates had significantly higher drug ED50 (>130 mg/kg) than PZQ sensitive isolates with ED50's <100 mg/kg. Moreover, in response to PZQ they were found to possess significant reductions in their worm muscle t...Continue Reading

Citations

Mar 31, 2012·European Journal of Drug Metabolism and Pharmacokinetics·Naglaa El-LakkanyLamia Heikal
Aug 19, 2009·PLoS Neglected Tropical Diseases·Sandra D MelmanEric S Loker
Dec 19, 2012·Parasitology International·John D ChanJonathan S Marchant
Apr 7, 2006·Expert Review of Anti-infective Therapy·Michael J Doenhoff, Livia Pica-Mattoccia
Oct 1, 2007·Expert Opinion on Drug Discovery·Sanaa S Botros, James L Bennett
Dec 28, 2004·International Journal for Parasitology·Robert M Greenberg
Jun 1, 2005·International Journal for Parasitology·Sanaa BotrosTim A Day
Mar 8, 2017·Antimicrobial Agents and Chemotherapy·Nuno ValeJosé M Correia da Costa
May 1, 2012·PLoS Neglected Tropical Diseases·James S McCarthyMaría-Gloria Basáñez
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Mar 11, 2019·International Immunopharmacology·Miriam Viviane DiasRômulo Dias Novaes
Dec 23, 2021·Science Translational Medicine·Sang-Kyu ParkJonathan S Marchant

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