Hostname: page-component-586b7cd67f-gb8f7 Total loading time: 0 Render date: 2024-11-25T21:00:00.823Z Has data issue: false hasContentIssue false
  • English
  • Français

Biotransformation of anthelmintics and the activity of drug-metabolizing enzymes in the tapeworm Moniezia expansa

Published online by Cambridge University Press:  06 November 2014

LUKÁŠ PRCHAL ,
HANA BÁRTÍKOVÁ ,
ANETA BEČANOVÁ ,
ROBERT JIRÁSKO ,
IVAN VOKŘÁL ,
LUCIE STUCHLÍKOVÁ ,
LENKA SKÁLOVÁ ,
VLADIMÍR KUBÍČEK ,
JIŘÍ LAMKA  and
FRANTIŠEK TREJTNAR
...Show all authors
LUKÁŠ PRCHAL
Affiliation:
Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic
HANA BÁRTÍKOVÁ
Affiliation:
Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic
ANETA BEČANOVÁ
Affiliation:
Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic
ROBERT JIRÁSKO
Affiliation:
Faculty of Chemical Technology, University of Pardubice, Studentská 573, CZ-53210 Pardubice, Czech Republic
IVAN VOKŘÁL
Affiliation:
Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic
LUCIE STUCHLÍKOVÁ
Affiliation:
Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic
LENKA SKÁLOVÁ
Affiliation:
Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic
VLADIMÍR KUBÍČEK
Affiliation:
Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic
JIŘÍ LAMKA
Affiliation:
Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic
FRANTIŠEK TREJTNAR
Affiliation:
Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic
BARBORA SZOTÁKOVÁ*
Affiliation:
Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic
*
* Corresponding author. Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic. E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Summary

The sheep tapeworm Moniezia expansa is very common parasite, which affects ruminants such as sheep, goats as well as other species. The benzimidazole anthelmintics albendazole (ABZ), flubendazole (FLU) and mebendazole (MBZ) are often used to treat the infection. The drug-metabolizing enzymes of helminths may alter the potency of anthelmintic treatment. The aim of our study was to assess the activity of the main drug-metabolizing enzymes and evaluate the metabolism of selected anthelmintics (ABZ, MBZ and FLU) in M. expansa. Activities of biotransformation enzymes were determined in subcellular fractions. Metabolites of the anthelmintics were detected and identified using high performance liquid chromatography/ultra-violet/VIS/fluorescence or ultra-high performance liquid chromatography/mass spectrometry. Reduction of MBZ, FLU and oxidation of ABZ were proved as well as activities of various metabolizing enzymes. Despite the fact that the conjugation enzymes glutathione S-transferase, UDP-glucuronosyl transferase and UDP-glucosyl transferase were active in vitro, no conjugated metabolites of anthelmintics were identified either ex vivo or in vitro. The obtained results indicate that sheep tapeworm is able to deactivate the administered anthelmintics, and thus protects itself against their action.

Keywords

Monieziadrug metabolismanthelminticbenzimidazolealbendazole
Type
Research Article
Information
Parasitology , Volume 142 , Issue 5 , April 2015 , pp. 648 - 659
Check for updates
Copyright
Copyright © Cambridge University Press 2014 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Akkaya, H., Deniz, A., Veren, D. and Esatgil, M. U. (2006). Field trials on the efficacy of praziquantel for treating monieziosis in naturally infected sheep. Medycyna Weterynaryjna 62, 278–280.Google Scholar
Alvarez, L. I., Solana, H. D., Mottier, M. L., Virkel, G. L., Fairweather, I. and Lanusse, C. E. (2005). Altered drug influx/efflux and enhanced metabolic activity in triclabendazole-resistant liver flukes. Parasitology 131, 501–510.Google Scholar
Barrett, J. (1998). Cytochrome P450 in parasitic protozoa and helminths. Comparative Biochemistry and Physiology Part C: Pharmacology, Toxicology and Endocrinology 121, 181–183.Google ScholarPubMed
Barrett, J. (1997). Helminth detoxification mechanisms. Journal of Helminthology 71, 85.Google Scholar
Bártíková, H., Krízová, V., Lamka, J., Kubícek, V., Skálová, L. and Szotáková, B. (2010 a). Flubendazole metabolism and biotransformation enzymes activities in healthy sheep and sheep with haemonchosis. Journal of Veterinary Pharmacology and Therapeutics 33, 56–62.Google Scholar
Bártíková, H., Vokřál, I., Skálová, L., Lamka, J. and Szotáková, B. (2010 b). In vitro oxidative metabolism of xenobiotics in the lancet fluke (Dicrocoelium dendriticum) and the effects of albendazole and albendazole sulphoxide ex vivo . Xenobiotica 40, 593–601.Google Scholar
Bártíková, H., Vokřál, I., Skálová, L., Kubíček, V., Firbasová, J., Briestenský, D., Lamka, J. and Szotáková, B. (2012). The activity of drug-metabolizing enzymes and the biotransformation of selected anthelmintics in the model tapeworm Hymenolepis diminuta . Parasitology 139, 809–818.CrossRefGoogle ScholarPubMed
Bauer, C. (1990). Comparative efficacy of praziquantel, albendazole, febantel and oxfendazole against Moniezia expansa . The Veterinary Record 127, 353–354.Google Scholar
Berriman, M., Haas, B. J., LoVerde, P. T., Wilson, R. A., Dillon, G. P., Cerqueira, G. C., Mashiyama, S. T., Al-Lazikani, B., Andrade, L. F., Ashton, P. D., Aslett, M. A., Bartholomeu, D. C., Blandin, G., Caffrey, C. R., Coghlan, A., Coulson, R., Day, T. A., Delcher, A., DeMarco, R., Djikeng, A., Eyre, T., Gamble, J. A., Ghedin, E., Gu, Y., Hertz-Fowler, C., Hirai, H., Hirai, Y., Houston, R., Ivens, A., Johnston, D. A. et al. (2009). The genome of the blood fluke Schistosoma mansoni . Nature 460, 352–358.Google Scholar
Bonilla, M., Denicola, A., Novoselov, S. V., Turanov, A. A., Protasio, A., Izmendi, D., Gladyshev, V. N. and Salinas, G. (2008). Platyhelminth mitochondrial and cytosolic redox homeostasis is controlled by a single thioredoxin glutathione reductase and dependent on selenium and glutathione. The Journal of Biological Chemistry 283, 17898–17907.CrossRefGoogle ScholarPubMed
Brophy, P. M., Southant, C. and Barrett, J. (1989). Glutathione transferases in the tapeworm Moniezia expansa . The Biochemical Journal 262, 939–946.CrossRefGoogle ScholarPubMed
Brophy, P. M., MacKintosh, N. and Morphew, R. M. (2012). Anthelmintic metabolism in parasitic helminths: proteomic insights. Parasitology 139, 1205–1217.CrossRefGoogle ScholarPubMed
Burke, M. D., Thompson, S., Weaver, R. J., Wolf, C. R. and Mayers, R. T. (1994). Cytochrome P450 specificities of alkoxyresorufin O-dealkylation in human and rat liver. Biochemical Pharmacology 48, 923–936.CrossRefGoogle ScholarPubMed
C. elegans Sequencing Consortium (1998). Genome sequence of the nematode C. elegans: a platform for investigating biology. Science 282, 2012–2018.CrossRefGoogle Scholar
Cashman, J. R. and Hanzlik, R. P. (1981). Microsomal oxidation of thiobenzamide. A photometric assay for the flavin-containing monooxygenase. Biochemical and Biophysical Research Communications 98, 147–153.Google Scholar
Ceballos, L., Elissondo, C., Sánchez Bruni, S., Denegri, G., Lanusse, C. and Alvarez, L. (2011). Comparative performances of flubendazole and albendazole in cystic echinococcosis: ex vivo activity, plasma/cyst disposition, and efficacy in infected mice. Antimicrobial Agents and Chemotherapy 55, 5861–5867.Google Scholar
Cvilink, V., Kubíček, V., Nobilis, M., Krízová, V., Szotáková, B., Lamka, J., Várady, M., Kubenová, M., Novotná, R., Gavelová, M. and Skálová, L. (2008 a). Biotransformation of flubendazole and selected model xenobiotics in Haemonchus contortus . Veterinary Parasitology 151, 242–248.Google Scholar
Cvilink, V., Skálová, L., Szotáková, B., Lamka, J., Kostiainen, R. and Ketola, R. A (2008 b). LC-MS-MS identification of albendazole and flubendazole metabolites formed ex vivo by Haemonchus contortus . Analytical and Bioanalytical Chemistry 391, 337–343.CrossRefGoogle ScholarPubMed
Cvilink, V., Lamka, J. and Skálová, L. (2009 a). Xenobiotic metabolizing enzymes and metabolism of anthelmintics in helminths. Drug Metabolism Reviews 41, 8–26.Google Scholar
Cvilink, V., Szotáková, B., Krízová, V., Lamka, J. and Skálová, L. (2009 b). Phase I biotransformation of albendazole in lancet fluke (Dicrocoelium dendriticum). Research in Veterinary Science 86, 49–55.Google Scholar
Dayan, A. D. (2003). Albendazole, mebendazole and praziquantel. Review of non-clinical toxicity and pharmacokinetics. Acta Tropica 86, 141–159.Google Scholar
Douch, P. G. and Blair, S. S. (1975). The metabolism of foreign compounds in the cestode, Moniezia expansa, and the nematode, Ascaris lumbricoides var suum. Xenobiotica 5, 279–292.CrossRefGoogle Scholar
Douch, P. G. and Buchanan, L. L. (1978). Glutathione Conjugation of some Xenobiotics by Ascaris suum and Moniezia expansa . Xenobiotica 8, 171–176.Google Scholar
Elliott, D. C. (1984). Tapeworm (Moniezia expansa) in sheep: anthelmintic treatment studies to assess possible pathogenic effects and production loss in young infected animals in the field. New Zealand Veterinary Journal 32, 185–188.CrossRefGoogle ScholarPubMed
Góth, L. (1991). A simple method for determination of serum catalase activity and revision of reference range. Clinica Chimica Acta 196, 143–151.Google Scholar
Habig, W. H. and Jakoby, W. B. (1981). Glutathione S-transferases (rat and human). Methods in Enzymology 77, 218–231.Google Scholar
Holčapek, M., Jirásko, R. and Lísa, M. (2010). Basic rules for the interpretation of atmospheric pressure ionization mass spectra of small molecules. Journal of Chromatography A 1217, 3908–3921.Google Scholar
Kotze, A. C. (1997). Cytochrome P450 monooxygenase activity in Haemonchus contortus (Nematoda). International Journal for Parasitology 27, 33–40.Google Scholar
Kotze, A. C. (1999). Peroxide-supported in-vitro cytochrome P450 activities in Haemonchus contortus . International Journal for Parasitology 29, 389–396.Google Scholar
Kuntz, A. N., Davioud-Charvet, E., Sayed, A. A, Califf, L. L., Dessolin, J., Arnér, E. S. J. and Williams, D. L. (2007). Thioredoxin glutathione reductase from Schistosoma mansoni: an essential parasite enzyme and a key drug target. PLoS Medicine 4, e206.Google Scholar
Laing, R., Kikuchi, T., Martinelli, A., Tsai, I. J., Beech, R. N., Redman, E., Holroyd, N., Bartley, D. J., Beasley, H., Britton, C., Curran, D., Devaney, E., Gilabert, A., Hunt, M., Jackson, F., Johnston, S. L., Kryukov, I., Li, K., Morrison, A. A., Reid, A. J., Sargison, N., Saunders, G. I., Wasmuth, J. D., Wolstenholme, A., Berriman, M., Gilleard, J. S. and Cotton, J. A. (2013). The genome and transcriptome of Haemonchus contortus, a key model parasite for drug and vaccine discovery. Genome Biology 14, R88.CrossRefGoogle ScholarPubMed
Mahin, L., Chadli, M. and Id Sidi Yahya, K. (1991). Treatment against monieziasis by suckling lambs deserves precedence versus trichostrongylosis under extensive conditions in Morocco. Tropicultura 9, 177–180.Google Scholar
Mamani-Linares, L. L. W. (2009). Anthelminthic resistance (Moniezia expansa, Moniezia benedeni and Thysanosoma actioides) in sheep against albendazole and febendazole in three farms of La Paz – Bolivia. REDVET 10, 1–13.Google Scholar
Maser, E. (1995). Xenobiotic carbonyl reduction and physiological steroid oxidoreduction. The pluripotency of several hydroxysteroid dehydrogenases. Biochemical Pharmacology 49, 421–440.Google Scholar
Mason, P., Moffat, J. R. and Cole, D. (2002). Tapeworm in sheep revisited. Proceedings of the Society of Sheep and Beef Cattle Veterinarians of the New Zealand Veterinary Association Annual Sem, 36, 147–151.Google Scholar
Maté, L., Virkel, G., Lifschitz, A., Ballent, M. and Lanusse, C. (2008). Hepatic and extra-hepatic metabolic pathways involved in flubendazole biotransformation in sheep. Biochemical Pharmacology 76, 773–783.Google Scholar
McCallum, M. J. and Barrett, J. (1995). The purification and properties of glutathione reductase from the cestode Moniezia expansa . The International Journal of Biochemistry and Cell Biology 27, 393–401.CrossRefGoogle ScholarPubMed
McKellar, Q. A. and Jackson, F. (2004). Veterinary anthelmintics: old and new. Trends in Parasitology 20, 456–461.Google Scholar
Mizuma, T., Machida, M., Hayashi, M. and Awazu, S. (1982). Correlation of drug conjugative metabolism rates between in vivo and in vitro: glucuronidation and sulfation of p-nitrophenol as a model compound in rat. Journal of Pharmacobio-Dynamics 5, 811–817.Google Scholar
Ohara, H., Miyabe, Y., Deyashiki, Y., Matsuura, K. and Kara, A. (1995). Reduction of drug ketones by dihydrodiol dehydrogenases, carbonyl reductase and aldehyde reductase of human liver. Biochemical Pharmacology 50, 221–227.CrossRefGoogle ScholarPubMed
Palackal, N. T., Burczynski, M. E., Harvey, R. G. and Penning, T. M. (2001). Metabolic activation of polycyclic aromatic hydrocarbon trans-dihydrodiols by ubiquitously expressed aldehyde reductase (AKR1A1). Chemico-Biological Interactions 130–132, 815–824.CrossRefGoogle ScholarPubMed
Paul, J. M. and Barrett, J. (1980). Peroxide metabolism in the cestodes Hymenolepis diminuta and Moniezia expansa . International Journal for Parasitology 10, 121–124.Google Scholar
Pérez, F. (2002). Ascorbic acid and flavonoid-peroxidase reaction as a detoxifying system of H2O2 in grapevine leaves. Phytochemistry 60, 573–580.Google Scholar
Saeed, H. M., Mostafa, M. H., O'Connor, P. J., Rafferty, J. A and Doenhoff, M. J. (2002). Evidence for the presence of active cytochrome P450 systems in Schistosoma mansoni and Schistosoma haematobium adult worms. FEBS Letters 519, 205–209.Google Scholar
Sanchez-Moreno, M., Orteoa, J. E., Sanchez-Navas, A., Salas-Peregrin, J. M. and Monteoliva, M. (1989). Cu-Zn-superoxide dismutase activity in Moniezia expansa: inhibition by pyrimidine derivatives. International Journal for Parasitology 19, 743–748.Google Scholar
Schistosoma japonicum Genome Sequencing and Functional Analysis Consortium (2009). The Schistosoma japonicum genome reveals features of host-parasite interplay. Nature 460, 345–351.Google Scholar
Smith, P. K., Krohn, R. I., Hermanson, G. T., Mallia, A. K., Gartner, F. H., Provenzano, M. D., Fujimoto, E. K., Goeke, N. M., Olson, B. J. and Klenk, D. C. (1985). Measurement of protein using bicinchoninic acid. Analytical Biochemistry 150, 76–85.CrossRefGoogle ScholarPubMed
Solana, H. D., Rodriguez, J. A. and Lanusse, C. E. (2001). Comparative metabolism of albendazole and albendazole sulphoxide by different helminth parasites. Parasitology Research 87, 275–280.Google Scholar
Solana, H. D., Scarcella, S., Virkel, G., Ceriani, C., Rodríguez, J. and Lanusse, C. (2009). Albendazole enantiomeric metabolism and binding to cytosolic proteins in the liver fluke Fasciola hepatica . Veterinary Research Communications 33, 163–173.CrossRefGoogle ScholarPubMed
Southworth, J., Harvey, C. and Larson, S. (1996). Use of praziquantel for the control of Moniezia expansa in lambs. New Zealand Veterinary Journal 44, 112–115.CrossRefGoogle ScholarPubMed
Stuchlíková, L., Jirásko, R., Vokřál, I., Lamka, J., Špulák, M., Holčapek, M., Szotáková, B., Bártíková, H., Pour, M. and Skálová, L. (2013). Investigation of the metabolism of monepantel in ovine hepatocytes by UHPLC/MS/MS. Analytical and Bioanalytical Chemistry 405, 1705–1712.Google Scholar
Tsai, I. J., Zarowiecki, M., Holroyd, N., Garciarrubio, A., Sanchez-Flores, A., Brooks, K. L., Tracey, A., Bobes, R. J., Fragoso, G., Sciutto, E., Aslett, M., Beasley, H., Bennett, H. M., Cai, J., Camicia, F., Clark, R., Cucher, M., De Silva, N., Day, T. A., Deplazes, P., Estrada, K., Fernández, C., Holland, P. W. H., Hou, J., Hu, S., Huckvale, T., Hung, S. S., Kamenetzky, L., Keane, J. A., Kiss, F. et al. (2013). The genomes of four tapeworm species reveal adaptations to parasitism. Nature 496, 57–63.Google Scholar
Vokřál, I., Bártíková, H., Prchal, L., Stuchlíková, L., Skálová, L., Szotáková, B., Lamka, J., Várady, M. and Kubíček, V. (2012). The metabolism of flubendazole and the activities of selected biotransformation enzymes in Haemonchus contortus strains susceptible and resistant to anthelmintics. Parasitology 139, 1309–1316.Google Scholar
Vokřál, I., Jirásko, R., Stuchlíková, L., Bártíková, H., Szotáková, B., Lamka, J., Várady, M. and Skálová, L. (2013). Biotransformation of albendazole and activities of selected detoxification enzymes in Haemonchus contortus strains susceptible and resistant to anthelmintics. Veterinary Parasitology 196, 373–381.Google Scholar
Wolstenholme, A. J., Fairweather, I., Prichard, R., von Samson-Himmelstjerna, G. and Sangster, N. C. (2004). Drug resistance in veterinary helminths. Trends in Parasitology 20, 469–476.Google Scholar