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Albendazole enantiomeric metabolism and binding to cytosolic proteins in the liver fluke Fasciola hepatica

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Abstract

Fascioliasis causes important economic losses in ruminant species all over the world. Its control is largely based on the use of the flukicidal compound triclabendazole (TCBZ). However, its chemically related benzimidazole anthelmintic albendazole (ABZ) is being successfully used to control TCBZ-resistance flukes. This research gains some insights into the comparative molecular behaviour of both anthelmintics within the target fluke. The goals of the current work were: (i) to assess the competitive binding of ABZ and TCBZ to cytosolic proteins of F. hepatica, and (ii) to evaluate the enantioselective biotransformation of ABZ in microsomal fractions obtained from TCBZ-susceptible and TCBZ-resistant strains of the liver fluke. Cytosolic proteins from fluke specimens bound TCBZ with greater affinity (83%) than ABZ (44%) and the fraction of TCBZ bound to cytosolic proteins was not displaced by ABZ. The microsomes from both -susceptible and resistant flukes sulphoxidized ABZ into ABZ sulphoxide (ABZSO). However, this oxidative activity was 49% higher in microsomes from TCBZ-resistant flukes (P < 0.001) with a predominant production of the (+) ABZSO enantiomer. As earlier shown for TCBZ, the results reported here confirm an enhanced ability for ABZ oxidation in TCBZ-resistant flukes. While this enhanced oxidative metabolism of ABZ may cooperate to the resistance phenomenon, other pharmacodynamic-based mechanisms may be involved, which would explain why, although being chemically-related, ABZ remains efficacious against TCBZ resistant flukes under field conditions.

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Acknowledgements

Liver fluke metacercariae were provided by Professor I. Fairweather, School of Biology and Biochemistry, The Queens University of Belfast, Northern Ireland, UK. H. Solana is Adjunct Professional from the Comisión de Investigaciones Científicas (CIC) de la Provincia de Buenos Aires, Argentina. Research at the Laboratorio de Biología Celular y Molecular and Laboratorio de Farmacología is supported by CONICET, Universidad Nacional del Centro and Agencia Nacional de Promoción Científica y Tecnológica (PICT BID 1728/ OC-AR N° 38054) (all Argentina).

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Authors and Affiliations

  1. Lab. Biología Celular y Molecular, Dpto. de Cs. Biológicas, FCV-UNICEN, Campus Universitario, Tandil, Argentina

    H. Solana, S. Scarcella, C. Ceriani & J. Rodríguez

  2. Lab. de Farmacología, Dpto. de Fisiopatología. FCV-UNICEN, Campus Universitario, Tandil, Argentina

    G. Virkel & C. Lanusse

Authors
  1. H. Solana
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  2. S. Scarcella
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  3. G. Virkel
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  4. C. Ceriani
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  5. J. Rodríguez
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  6. C. Lanusse
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Correspondence to H. Solana.

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Solana, H., Scarcella, S., Virkel, G. et al. Albendazole enantiomeric metabolism and binding to cytosolic proteins in the liver fluke Fasciola hepatica . Vet Res Commun 33, 163–173 (2009). https://doi.org/10.1007/s11259-008-9166-3

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  • DOI: https://doi.org/10.1007/s11259-008-9166-3

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