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A Potential Novel Anthelmintic? The Cysteine Proteases Show Potent Anthelmintic Activity Against Cyathostomins In Vitro
Author(s) -
Peachey L.,
Matthews J.,
Pinchbeck G.,
Behnke J.,
Burden F.,
Hodgkinson J.
Publication year - 2014
Publication title -
equine veterinary journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.82
H-Index - 87
eISSN - 2042-3306
pISSN - 0425-1644
DOI - 10.1111/evj.12323_52
Subject(s) - anthelmintic , in vivo , biology , veterinary medicine , donkey , proteases , larva , papain , pharmacology , medicine , microbiology and biotechnology , zoology , biochemistry , enzyme , ecology
Reasons for performing study Anthelmintic resistance is a global problem and constitutes a major threat to the welfare of equids worldwide. The cyathostomins are the most numerous and pathogenic gastrointestinal nematode ( GIN ) of equids in the developed world. Cyathostomins show widespread resistance to 2 out of 3 of the major classes of anthelmintic and recently there are reports of reduced efficacy to the potent macrocyclic lactones ( MLs ). None of the 3 novel classes of anthelmintic that have emerged in the last decade are licensed for use in equids. The cysteine proteases ( CPs ) are plant proteins that have shown potent activity against GINs in vivo in sheep and pigs. Objectives This study aimed to evaluate the anthelmintic effect of the CP papain on cyathostomins in vitro using the egg hatch assay ( EHA ) and larval migration inhibition test ( LMIT ). Methods Samples of cyathostomin eggs and third stage larvae were collected and cultured from a population of equids that have recently shown reduced ML efficacy in vivo . The EHA and LMIT were performed on repeated samples with increasing concentrations of papain. Dose–response curves were plotted and PROBIT analysis performed on the data to give EC ‐50 values (concentration that gives 50% of the maximal response). Results Papain caused a dose dependent inhibition of both egg hatch and larval migration. The EC ‐50 values were 2 μmol/l and 100 μmol/l in the EHA and LMIT respectively, indicating a more potent effect on egg hatch. Conclusions The CP papain shows potent anthelmintic activity against cyathostomins in vitro . Good evidence of anthelmintic effect against GINs in other host species is supportive of its potential use in equids. Further work is indicated to evaluate safety and in vivo efficacy. Ethical animal research: The study was approved by the University of L iverpool and Donkey Sanctuary Ethics Committee. Explicit owner informed consent for participation in this study was not stated. Sources of funding: The Donkey Sanctuary, University of L iverpool – Institute of Infection and Global Health. Competing interests: None.