Antischistosomal activity of a calcium channel
antagonist on schistosomula and adult Schistosoma mansoni
worms |
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Authors: | Vanessa Silva-Moraes Flávia Fernanda Bubula Couto Marah Mileib Vasconcelos Neusa Araújo Paulo Marcos Zech Coelho Naftale Katz Rafaella Fortini Queiroz Grenfell |
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Institution: | 1. Laboratório de Esquistossomose, Centro de Pesquisas René Rachou-Fiocruz, Belo Horizonte, MG, Brasil ;2. Escola de Farmácia, Universidade de Itaúna, Itaúna, MG, Brasil ;3. Universidade Federal de São João Del Rey, Divinópolis, MG, Brasil |
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Abstract: | Current schistosomiasis control strategies are largely based on chemotherapeutic
agents and a limited number of drugs are available today. Praziquantel (PZQ) is
the only drug currently used in schistosomiasis control programs. Unfortunately,
this drug shows poor efficacy in patients during the earliest infection phases.
The effects of PZQ appear to operate on the voltage-operated Ca2+channels, which
are located on the external Schistosoma mansoni membrane.
Because some Ca2+channels have dihydropyridine drug class (a class that includes
nifedipine) sensitivity, an in vitro analysis using a calcium channel antagonist
(clinically used for cardiovascular hypertension) was performed to determine the
antischistosomal effects of nifedipine on schistosomula and adult worm cultures.
Nifedipine demonstrated antischistosomal activity against schistosomula and
significantly reduced viability at all of the concentrations used alone or in
combination with PZQ. In contrast, PZQ did not show significant efficacy when
used alone. Adult worms were also affected by nifedipine after a 24 h incubation
and exhibited impaired motility, several lesions on the tegument and intense
contractility. These data support the idea of Ca2+channels subunits as drug
targets and favour alternative therapeutic schemes when drug resistance has been
reported. In this paper, strong arguments encouraging drug research are
presented, with a focus on exploring schistosomal Ca2+channels. |
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Keywords: | Schistosoma mansoni antischistosomal drugs calcium channels antagonists L-type calcium channels nifedipine |
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