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Host genetic influences on the anthelmintic efficacy of papaya-derived cysteine proteinases in mice

  • WENCESLAUS LUOGA (a1) (a2), FADLUL MANSUR (a1) (a3), GILLIAN STEPEK (a1), ANN LOWE (a1), IAN R. DUCE (a1), DAVID. J. BUTTLE (a4) and JERZY M. BEHNKE (a1)...

Summary

Eight strains of mice, of contrasting genotypes, infected with Heligmosomoides bakeri were studied to determine whether the anthelmintic efficacy of papaya latex varied between inbred mouse strains and therefore whether there is an underlying genetic influence on the effectiveness of removing the intestinal nematode. Infected mice were treated with 330 nmol of crude papaya latex or with 240 nmol of papaya latex supernatant (PLS). Wide variation of response between different mouse strains was detected. Treatment was most effective in C3H (90·5–99·3% reduction in worm counts) and least effective in CD1 and BALB/c strains (36·0 and 40·5%, respectively). Cimetidine treatment did not improve anthelmintic efficacy of PLS in a poor drug responder mouse strain. Trypsin activity, pH and PLS activity did not differ significantly along the length of the gastro-intestinal (GI) tract between poor (BALB/c) and high (C3H) drug responder mouse strains. Our data indicate that there is a genetic component explaining between-mouse variation in the efficacy of a standard dose of PLS in removing worms, and therefore warrant some caution in developing this therapy for wider scale use in the livestock industry, and even in human medicine.

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Corresponding author

* Correspondence author. School of Life Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, UK. E-mail: jerzy.behnke@nottingham.ac.uk

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Present address: Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, Bearsden Road, Glasgow, G61 1QH, UK

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References

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Alving, A. S., Carson, P. E., Flanagan, C. L. and Ickes, C. E. (1956). Enzymatic deficiency in primaquine-sensitive erythrocytes. Science 124, 484485.
Barrett, A. J., Kembhavi, A. A. and Hanada, K. (1981). E-64 [L-trans-epoxysuccinyl-leucyl-amido (4-guanidino)butane] and related epoxides as inhibitors of cysteine proteinases. Acta Biologica et Medica Germanica 40, 15131517.
Behnke, J. and Harris, P. D. (2010). Heligmosomoides bakeri: a new name for an old worm? Trends Parasitology 26, 524529.
Behnke, J. M. and Parish, H. A. (1979). Nematospiroides dubius: arrested development of larvae in immune mice. Experimental Parasitology 47, 116127.
Behnke, J. M. and Robinson, M. (1985). Genetic control of immunity to Nematospiroides dubius: a 9-day anthelmintic abbreviated immunizing regime which separates weak and strong responder strains of mice. Parasite Immunology 7, 235253.
Behnke, J. M., Buttle, D. J., Stepek, G., Lowe, A. and Duce, I. R. (2008). Developing novel anthelmintics from plant cysteine proteinases. Parasites and Vectors 1, 29.
Bosch, T. M. (2008). Pharmacogenomics of drug-metabolizing enzymes and drug transporters in chemotherapy. Methods in Molecular Biology 448, 6376.
Buttle, D. J., Dando, P. M., Coe, P. F., Sharp, S. L., Shepherd, S. T. and Barrett, A. J. (1990). The preparation of fully active chymopapain free of contaminating proteinases. Biological Chemistry Hoppe-Seyler 371, 10831088.
Buttle, D. J., Behnke, J. M., Bartley, Y., Elsheikha, H. M., Bartley, D. J., Garnett, M. C., Donnan, A. A., Jackson, F., Lowe, A. and Duce, I. R. (2011). Oral dosing with papaya latex is an effective anthelmintic treatment for sheep infected with Haemonchus contortus . Parasites and Vectors 4, 36.
Cable, J., Harris, P. D., Lewis, J. W. and Behnke, J. M. (2006). Molecular evidence that Heligmosomoides polygyrus from laboratory mice and wood mice are separate species. Parasitology 133, 111122.
Didion, J. P. and de Villena, P. -M. (2014). Deconstructing Mus gemischus: advances in understanding ancestry, structure, and variation in the genome of the laboratory mouse. Mammalian Genome 24, 120.
Evans, W. E. and Johnson, J. A. (2001). Pharmacogenetics: the inherited basis for interindividual differences in drug response. Annual Review of Genomics and Human Genetics 2, 939.
Evans, W. E. and Relling, M. V. (2004). Moving towards individualized medicine with pharmacogenomics. Nature 429, 464468.
Huet, J., Looze, Y., Bartik, K., Raussens, V., Wintjens, R. and Boussard, P. (2006). Structural characterization of the papaya cysteine proteinases at low pH. Biochemical and Biophysical Research Communication 341, 620626.
Levecke, B., Buttle, D. J., Behnke, J. M., Duce, I. R. and Vercruysse, J. (2014). Cysteine proteinases from papaya (Carica papaya) in the treatment of experimental Trichuris suis infection in pigs: two randomized controlled trials. Parasites and Vectors 7, 255.
Luoga, W., Mansur, F., Buttle, D. J., Duce, I. R., Garnett, M. C. and Behnke, J. M. (2012). The anthelmintic efficacy of papaya latex in a rodent-nematode model is not dependent on fasting before treatment. Journal of Helminthology 86, 311316.
Mansur, F., Luoga, W., Buttle, D. J., Duce, I. R., Lowe, A. and Behnke, J. M. (2014). The anthelmintic efficacy of natural plant cysteine proteinases against two rodent cestodes Hymenolepis diminuta and Hymenolepis microstoma in vitro . Veterinary Parasitology 201, 4858.
McConnell, E. L., Basit, A. W. and Murdan, S. (2008). Measurements of rat and mouse gastrointestinal pH, fluid and lymphoid tissue, and implications for in-vivo experiments. Journal of Pharmacology and Pharmacotherapeutics 60, 6370.
Mole, J. E. and Horton, H. R. (1973). Kinetics of papain-catalyzed hydrolysis of α-N-benzoyl-L-arginine-p-nitroanilide. Biochemistry 12, 816822.
Robinson, M., Wahid, F. N., Behnke, J. M. and Gilbert, F. S. (1989). Immunological relationships during primary infection with Heligmosomoides polygyrus (Nematospiroides dubius): dose-dependent expulsion of adult worms. Parasitology 98, 115124.
Satrija, F., Nansen, P., Murtini, S. and He, S. (1995). Anthelmintic activity of papaya latex against patent Heligmosomoides polygyrus infections in mice. Journal of Ethnopharmacology 48, 161164.
Smith, C. J., Rocha, E. R. and Paster, B. J. (2006). In: The medically important Bacteroides spp. health and disease. The Prokaryotes. (eds Dworkin, M., Falkow, S., Rosenberg, E., Schleifer, K. H., Stackebrandt, E.), 7, 381427. Springer-Verlag, New York.
Stepek, G., Lowe, A. E., Buttle, D. J., Duce, I. R. and Behnke, J. M. (2007 a). The anthelmintic efficacy of plant-derived cysteine proteinases against the rodent gastrointestinal nematode, Heligmosomoides polygyrus, in vivo . Parasitology 134, 14091419.
Stepek, G., Lowe, A. E., Buttle, D. J., Duce, I. R. and Behnke, J. M. (2007 b). Anthelmintic action of plant cysteine proteinases against the rodent stomach nematode, Protospirura muricola, in vitro and in vivo . Parasitology 134, 103112.
Tsang, S., Sun, Z., Luke, B., Stewart, C., Lum, N., Gregory, M., Wu, X., Subleski, M., Jenkins, N. A., Copeland, N. G. and Munroe, D. J. (2005). A comprehensive SNP-based genetic analysis of inbred mouse strains. Mammalian Genome 16, 476480.
Zucker, S., Buttle, D. J., Nicklin, M. J. H. and Barrett, A. J. (1985). The proteolytic activities of chymopapain, papain, and papaya proteinase III. Biochimica et Biophysica Acta (BBA) – Protein Structure and Molecular Enzymology 828, 196204.

Keywords

Host genetic influences on the anthelmintic efficacy of papaya-derived cysteine proteinases in mice

  • WENCESLAUS LUOGA (a1) (a2), FADLUL MANSUR (a1) (a3), GILLIAN STEPEK (a1), ANN LOWE (a1), IAN R. DUCE (a1), DAVID. J. BUTTLE (a4) and JERZY M. BEHNKE (a1)...

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