Hostname: page-component-848d4c4894-4hhp2 Total loading time: 0 Render date: 2024-05-17T02:52:47.547Z Has data issue: false hasContentIssue false
  • English
  • Français

Increased susceptibility of a triclabendazole (TCBZ)-resistant isolate of Fasciola hepatica to TCBZ following co-incubation in vitro with the P-glycoprotein inhibitor, R(+)-verapamil

Published online by Cambridge University Press:  12 June 2013

M. MEANEY ,
J. SAVAGE ,
G. P. BRENNAN ,
E. HOEY ,
A. TRUDGETT  and
I. FAIRWEATHER
M. MEANEY
Affiliation:
Parasite Therapeutics Research Group, School of Biological Sciences, Medical Biology Centre, The Queen's University of Belfast, 97 Lisburn Road, Belfast, BT9 7BL, Northern Ireland
J. SAVAGE
Affiliation:
Parasite Therapeutics Research Group, School of Biological Sciences, Medical Biology Centre, The Queen's University of Belfast, 97 Lisburn Road, Belfast, BT9 7BL, Northern Ireland
G. P. BRENNAN
Affiliation:
Parasite Therapeutics Research Group, School of Biological Sciences, Medical Biology Centre, The Queen's University of Belfast, 97 Lisburn Road, Belfast, BT9 7BL, Northern Ireland
E. HOEY
Affiliation:
Parasite Therapeutics Research Group, School of Biological Sciences, Medical Biology Centre, The Queen's University of Belfast, 97 Lisburn Road, Belfast, BT9 7BL, Northern Ireland
A. TRUDGETT
Affiliation:
Parasite Therapeutics Research Group, School of Biological Sciences, Medical Biology Centre, The Queen's University of Belfast, 97 Lisburn Road, Belfast, BT9 7BL, Northern Ireland
I. FAIRWEATHER*
Affiliation:
Parasite Therapeutics Research Group, School of Biological Sciences, Medical Biology Centre, The Queen's University of Belfast, 97 Lisburn Road, Belfast, BT9 7BL, Northern Ireland
*
*Corresponding author: School of Biological Sciences, Medical Biology Centre, The Queen's University of Belfast, 97 Lisburn Road, Belfast, BT9 7BL, Northern Ireland. E-mail: i.fairweather@qub.ac.uk
Get access Rights & Permissions [Opens in a new window]

Summary

A study was carried out to investigate whether the action of triclabendazole sulphoxide (TCBZ.SO) against the liver fluke, Fasciola hepatica is altered by inhibition of P-glycoprotein (Pgp)-linked drug efflux pumps. The Oberon TCBZ-resistant and Cullompton TCBZ-susceptible fluke isolates were used for this in vitro study and the Pgp inhibitor selected was R(+)-verapamil [R(+)-VPL]. For experiments with the Oberon isolate, flukes were incubated for 24 h with either R(+)-VPL (1×10−4m) on its own, TCBZ.SO (15 μg mL−1) alone, a combination of R(+)-VPL (1×10−4m) plus TCBZ.SO (15 μg mL−1), TCBZ.SO (50 μg mL−1) on its own, or a combination of TCBZ.SO (50 μg mL−1) plus R(+)-VPL (1×10−4m). They were also incubated in TCBZ.SO (50 μg mL−1) alone or in combination with R(+)-VPL (1×10−4m) until they became inactive; and in TCBZ.SO (50 μg mL−1) alone for a time to match that of the combination inactivity time. Flukes from the Cullompton isolate were treated with either TCBZ.SO (50 μg mL−1) alone or in combination with R(+)-VPL (1×10−4m) until they became inactive, or with TCBZ.SO (50 μg mL−1) alone time-matched to the combination inactivity time. Morphological changes resulting from drug treatment and following Pgp inhibition were assessed by means of scanning electron microscopy. Incubation in R(+)-VPL alone had a minimal effect on either isolate. TCBZ.SO treatment had a relatively greater impact on the TCBZ-susceptible Cullompton isolate. When R(+)-VPL was combined with TCBZ.SO in the incubation medium, however, the surface disruption to both isolates was more severe than that seen after TCBZ.SO treatment alone; also, the time taken to reach inactivity was shorter. More significantly, though, the potentiation of drug activity was greater in the Oberon isolate; also, it was more distinct at the higher concentration of TCBZ.SO. So, the Oberon isolate appears to be particularly sensitive to efflux pump inhibition. The results of this study suggest that enhanced drug efflux in the Oberon isolate may be involved in the mechanism of resistance to TCBZ.

Keywords

Fasciola hepaticaliver fluketriclabendazole resistanceR(+)-verapamilP-glycoprotein inhibitionscanning electron microscopy
Type
Research Article
Information
Parasitology , Volume 140 , Issue 10 , September 2013 , pp. 1287 - 1303
Copyright
Copyright © Cambridge University Press 2013 

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

REFERENCES

Alvarez, A. I., Merino, G., Molina, A. J., Pulido, M. M., McKellar, Q. A. and Prieto, J. G. (2006). Role of ABC transporters in veterinary drug research and parasite resistance. Current Drug Delivery 3, 199–206.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Alvinerie, M., Dupuy, J., Eeckhoutte, C. and Sutra, J. F. (1999). Enhanced absorption of pour-on ivermectin formulation in rats by co-administration of the multidrug-resistant-reversing agent verapamil. Parasitology Research 85, 920–922.CrossRefGoogle ScholarPubMed
Alvinerie, M., Dupuy, J., Kiki-Mvouaka, S., Sutra, J.-F. and Lespine, A. (2008). Ketoconazole increases the plasma levels of ivermectin in sheep. Veterinary Parasitology 157, 117–122.CrossRefGoogle ScholarPubMed
Ardelli, B. F. and Prichard, R. K. (2008). Effects of ivermectin and moxidectin on the transcription of genes coding for multidrug resistance associated proteins and behaviour in Caenorhabditis elegans. Journal of Nematology 40, 290–298.Google Scholar
Ardelli, B. F. and Prichard, R. K. (2013). Inhibition of P-glycoprotein enhances sensitivity of Caenorhabditis elegans to ivermectin. Veterinary Parasitology 191, 264–275.CrossRefGoogle ScholarPubMed
Bártíková, H., Vokřál, I., Skálová, L., Lamka, J. and Szotáková, B. (2010). 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.CrossRefGoogle ScholarPubMed
Bartley, D. J., Mc Allister, H., Bartley, Y., Dupuy, J., Menez, C., Alvinerie, M., Jackson, F. and Lespine, A. (2009). P-glycoprotein interfering agents potentiate ivermectin susceptibility in ivermectin sensitive and resistant isolates of Teladorsagia circumcinta and Haemonchus contortus. Parasitology 136, 1081–1088.CrossRefGoogle Scholar
Bartley, D. J., Morrison, A. A., Dupuy, J., Bartley, Y., Sutra, J. F., Menez, C., Alvineire, M., Jackson, F., Devin, L. and Lespine, A. (2012). Influence of Pluronic 85 and ketoconazole on disposition and efficacy of ivermectin in sheep infected with a multiple resistant Haemonchus contortus isolate. Veterinary Parasitology 187, 464–472.CrossRefGoogle ScholarPubMed
Beugnet, F., Gauthey, M. and Kerboeuf, D. (1997). Partial in vitro reversal of benzimidazole resistance by the free-living stages of Haemonchus contortus with verapamil. Veterinary Record 141, 575–576.CrossRefGoogle ScholarPubMed
Biscardi, M., Teodori, E., Caporale, R., Budriesi, R., Balestri, F., Scappini, B., Gavazzi, S. and Grossi, A. (2006). Multidrug reverting activity toward leukemia cells in a group of new verapamil analogues with low cardiovascular activity. Leukemia Research 30, 1–8.CrossRefGoogle Scholar
Bosch, I. B., Wang, Z.-X., Tao, L.-F. and Shoemaker, C. B. (1994). Two Schistosoma mansoni cDNAs encoding ATP-binding cassette (ABC) family proteins. Molecular and Biochemical Parasitology 65, 351–356.CrossRefGoogle ScholarPubMed
Broeks, A., Janssen, H. A., Calafat, J. and Plasterk, R. H. (1995). A P-glycoprotein protects Caenorhabditis elegans against natural toxins. EMBO Journal 9, 1858–1866.CrossRefGoogle Scholar
Choi, S. U., Lee, C. O., Kim, K. H., Choi, E. J., Park, S. H., Shin, H. S., Yoo, S. E., Jung, N. P. and Lee, B. H. (1998). Reversal of multidrug resistance by novel verapamil analogs in cancer cells. Anti-Cancer Drugs 9, 157–165.CrossRefGoogle ScholarPubMed
Coles, G. C. (1986). Anthelmintic activity of triclabendazole. Journal of Helminthology 60, 210–212.CrossRefGoogle ScholarPubMed
Cvilink, V., Lamka, J. and Skálová, L. (2009 a). Xenobiotic metabolizing enzymes and metabolism of anthelmintics in helminthes. Drug Metabolism Reviews 41, 8–26.CrossRefGoogle Scholar
Cvilink, V., Szotáková, B., Křižová, 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.CrossRefGoogle ScholarPubMed
Devine, C., Brennan, G. P., Lanusse, C. E., Alvarez, L. I., Trudgett, A., Hoey, E. and Fairweather, I. (2009). Effect of the metabolic inhibitor, methimazole on the drug susceptibility of a triclabendazole-resistant isolate of Fasciola hepatica. Parasitology 136, 183–192.CrossRefGoogle ScholarPubMed
Devine, C., Brennan, G. P., Lanusse, C. E., Alvarez, L. I., Trudgett, A., Hoey, E. and Fairweather, I. (2010 a). Inhibition of cytochrome P450-mediated metabolism enhances ex vivo susceptibility of Fasciola hepatica to triclabendazole. Parasitology 137, 871–880.CrossRefGoogle ScholarPubMed
Devine, C., Brennan, G. P., Lanusse, C. E., Alvarez, L. I., Trudgett, A., Hoey, E. and Fairweather, I. (2010 b). Potentiation of triclabendazole sulphoxide-induced tegumental disruption by methimazole in a triclabendazole-resistant isolate of Fasciola hepatica. Parasitology Research 106, 1351–1363.CrossRefGoogle Scholar
Devine, C., Brennan, G. P., Lanusse, C. E., Alvarez, L. I., Trudgett, A., Hoey, E. and Fairweather, I. (2010 c). Enhancement of the drug susceptibility of a triclabendazole-resistant isolate of Fasciola hepatica using the metabolic inhibitor ketoconazole. Parasitology Research 107, 337–353.CrossRefGoogle ScholarPubMed
Devine, C., Brennan, G. P., Lanusse, C. E., Alvarez, L. I., Trudgett, A., Hoey, E. M. and Fairweather, I. (2011 a). Piperonyl butoxide enhances triclabendazole action against triclabendazole-resistant Fasciola hepatica. Parasitology 138, 224–236.CrossRefGoogle ScholarPubMed
Devine, C., Brennan, G. P., Lanusse, C. E., Alvarez, L. I., Trudgett, A., Hoey, E. M. and Fairweather, I. (2011 b). Enhancement of triclabendazole action in vivo against a triclabendazole-resistant isolate of Fasciola hepatica by co-treatment with ketoconazole. Veterinary Parasitology 177, 305–315.CrossRefGoogle ScholarPubMed
Devine, C., Brennan, G. P., Lanusse, C. E., Alvarez, L. I., Trudgett, A., Hoey, E. and Fairweather, I. (2011 c). Inhibition of triclabendazole metabolism in vitro by ketoconazole increases disruption to the tegument of a triclabendazole-resistant isolate of Fasciola hepatica. Parasitology Research 109, 981–995.CrossRefGoogle Scholar
Devine, C., Brennan, G. P., Lanusse, C. E., Alvarez, L. I., Trudgett, A., Hoey, E. and Fairweather, I. (2011 d). Erratum to: inhibition of triclabendazole metabolism in vitro by ketoconazole increases disruption to the tegument of a triclabendazole-resistant isolate of Fasciola hepatica. Parasitology Research 109, 1209–1223.CrossRefGoogle Scholar
Devine, C., Brennan, G. P., Lanusse, C. E., Alvarez, L. I., Trudgett, A., Hoey, E. and Fairweather, I. (2012). Potentiation of triclabendazole action in vivo against a triclabendazole-resistant isolate of Fasciola hepatica following its co-administration with the metabolic inhibitor, ketoconazole. Veterinary Parasitology 184, 37–47.CrossRefGoogle ScholarPubMed
Dupuy, J., Larrieu, G., Sutra, J. F., Lespine, A. and Alvinerie, M. (2003). Enhancement of moxidectin bioavailability in lamb by a natural flavonoid: quercetin. Veterinary Parasitology 112, 337–347.CrossRefGoogle ScholarPubMed
Dupuy, J., Alvinerie, M., Ménez, C. and Lespine, A. (2010). Interaction of anthelmintic drugs with P-glycoprotein in recombinant LLC-PK1-mdr1a cells. Chemico-Biological Interactions 186, 280–286.CrossRefGoogle ScholarPubMed
Echizen, H., Brecht, T., Niedergesass, S., Vogelgesang, B. and Eichelbaum, M. (1985). The effect of dextro-, levo-, and racemic verapamil on atrioventricular conduction in humans. American Heart Journal 109, 210–217.CrossRefGoogle ScholarPubMed
Fairweather, I. (2005). Triclabendazole: new skills to unravel an old(ish) enigma. Journal of Helminthology 79, 227–234.CrossRefGoogle ScholarPubMed
Fairweather, I. (2011 a). Reducing the future threat from (liver) fluke: realistic prospect or quixotic fantasy? Veterinary Parasitology 180, 133–143.CrossRefGoogle ScholarPubMed
Fairweather, I. (2011 b). Raising the bar on reporting cases of ‘triclabendazole resistance’. Veterinary Record 168, 514–515.CrossRefGoogle Scholar
Fairweather, I. (2011 c). Liver fluke isolates: a question of provenance. Veterinary Parasitology 176, 1–8.CrossRefGoogle ScholarPubMed
Fairweather, I., Holmes, S. D. and Threadgold, L. T. (1983). Fasciola hepatica: a technique for monitoring in vitro motility. Experimental Parasitology 56, 369–380.CrossRefGoogle ScholarPubMed
Fairweather, I., Holmes, S. D. and Threadgold, L. T. (1984). Fasciola hepatica: motility response to fasciolicides in vitro. Experimental Parasitology 57, 209–224.CrossRefGoogle ScholarPubMed
Fairweather, I., Threadgold, L. T. and Hanna, R. E. B. (1999). Development of Fasciola hepatica in the mammalian host. In Fasciolosis (ed. Dalton, J. P.), pp. 47–111. CAB International, Wallingford, UK.Google Scholar
González-Canga, A., Fernández-Martínez, N., Sahagún-Prieto, A., Diez-Liébana, M. J., Sierra-Vega, M. and García-Vieitez, J. J. (2009). A review of the pharmacological interactions of ivermectin in several animal species. Current Drug Metabolism 10, 359–368.CrossRefGoogle ScholarPubMed
Guerrero, J. R. and Martin, S. S. (1984). Verapamil – full spectrum calcium channel blocking agent – an overview. Medicinal Research Reviews 4, 87–109.CrossRefGoogle ScholarPubMed
Halferty, L., O'Neill, J. F., Brennan, G. P., Keiser, J. and Fairweather, I. (2009). Electron microscopical study to assess the in vitro effects of the synthetic trioxolane OZ78 against the liver fluke, Fasciola hepatica. Parasitology 136, 1325–1337.CrossRefGoogle ScholarPubMed
Hennessy, D. R., Lacey, E., Steel, J. W. and Prichard, R. K. (1987). The kinetics of triclabendazole disposition in sheep. Journal of Veterinary Pharmacology and Therapeutics 10, 64–72.CrossRefGoogle ScholarPubMed
Hockerman, G. H., Peterson, B. Z., Johnson, B. D. and Catterall, W. A. (1997). Molecular determinants of drug binding and action on L-type calcium channels. Annual Review of Pharmacology and Toxicology 37, 361–396.CrossRefGoogle ScholarPubMed
Holmes, S. D. (1983). In vitro studies into the mode of action of anthelmintics on the liver fluke, Fasciola hepatica L. Ph.D. thesis, The Queen's University of Belfast, Northern Ireland.Google Scholar
Hugnet, C., Lespine, A. and Alvinerie, M. (2007). Multiple oral dosing of ketoconazole increases dog exposure to ivermectin. Journal of Pharmacy and Pharmaceutical Sciences 10, 311–318.Google ScholarPubMed
James, C. E. and Davey, M. W. (2009). Increased expression of ABC transport proteins is associated with ivermectin resistance in the model nematode Caenorhabditis elegans. International Journal for Parasitology 39, 213–220.CrossRefGoogle ScholarPubMed
James, C. E., Hudson, A. L. and Davey, M. W. (2009). An update on P-glycoprotein and drug resistance in Schistosoma mansoni. Trends in Parasitology 25, 538–539.CrossRefGoogle ScholarPubMed
Kageyama, M., Namiki, H., Fukushima, H., Ito, Y., Shibata, N. and Takada, K. (2005). In vivo effects of cyclosporin A and ketoconazole on the pharmacokinetics of representative substrates for P-glycoprotein and cytochrome P450 (CYP) 3A in rats. Biological and Pharmaceutical Bulletin 28, 316–322.CrossRefGoogle ScholarPubMed
Kasinathan, R. S. and Greenberg, R. M. (2012). Pharmacology and potential physiological significance of schistosome multidrug resistance transporters. Experimental Parasitology 132, 2–6.CrossRefGoogle ScholarPubMed
Kasinathan, R. S., Goronga, T., Messerli, S. M., Webb, T. R. and Greenberg, R. M. (2010 a). Modulation of a Schistosoma mansoni multidrug transporter by the antischistosomal drug praziquantel. FASEB Journal 24, 128–135.CrossRefGoogle ScholarPubMed
Kasinathan, R. S., Morgan, W. M. and Greenberg, R. M. (2010 b). Schistosoma mansoni express higher levels of multidrug resistance-associated protein 1 (SmMRP1) in juvenile worms and in response to praziquantel. Molecular and Biochemical Parasitology 173, 25–31.CrossRefGoogle ScholarPubMed
Kasinathan, R. S., Morgan, W. M. and Greenberg, R. M. (2011). Genetic knockdown and pharmacological inhibition of parasite multidrug resistance transporters disrupts egg production in Schistosoma mansoni. PLoS Neglected Tropical Diseases 5, e1425.CrossRefGoogle ScholarPubMed
Kerboeuf, D. and Riou, M. (2011). Efflux pump inhibitors: a progress in parasitic nematode control. Bulletin de l'Académie Vétérinaire de France 164, 257–264.CrossRefGoogle Scholar
Kerboeuf, D., Blackhall, W., Kaminsky, R. and Von Samson-Himmelstjerna, G. (2003). P-glycoprotein in helminths: function and perspectives for anthelmintic treatment and reversal of resistance. International Journal of Antimicrobial Agents 22, 332–346.CrossRefGoogle ScholarPubMed
Kerboeuf, D., Riou, M., Neveu, C. and Issouf, M. (2010). Membrane transport in helminths. Anti-Infective Agents in Medicinal Chemistry 9, 113–129.CrossRefGoogle Scholar
Kim, R. B., Wandel, C., Leake, B., Cvetkovic, M., Fromm, M. F., Dempsye, P. J., Roden, M. M., Belas, F., Chaudhary, A. K., Roden, D. M., Wood, A. J. and Wilkinson, G. R. (1999). Interrelationship between substrates and inhibitors of human CYP3A and P-glycoprotein. Pharmaceutical Research 16, 408–414.Google ScholarPubMed
Kumkate, S., Chunchob, S. and Janvilisri, T. (2008). Expression of ATP-binding cassette multidrug transporters in the giant liver fluke Fasciola gigantica and their possible involvement in the transport of bile salts and anthelmintics. Molecular and Cellular Biochemistry 317, 77–84.CrossRefGoogle ScholarPubMed
Lespine, A., Alvinerie, M., Vercruysse, J., Prichard, R. K. and Geldhof, P. (2008). ABC transporter modulation: a strategy to enhance the activity of macrocyclic lactone anthelmintics. Trends in Parasitology 24, 293–298.CrossRefGoogle ScholarPubMed
Lespine, A., Dupuy, J., Alvinerie, M., Comera, C., Nagy, T., Krajcsi, P. and Orlowski, S. (2009). Interaction of macrocyclic lactones with the multidrug transporters: the bases of the pharmacokinetics of lipid-like drugs. Current Drug Metabolism 10, 272–288.CrossRefGoogle ScholarPubMed
Lespine, A., Ménez, C., Bourguinat, C. and Prichard, R. K. (2012). P-glycoproteins and other multidrug resistance transporters in the pharmacology of anthelmintics: prospects for reversing transport-dependent anthelmintic resistance. International Journal for Parasitology: Drugs and Drug Resistance 2, 58–75.Google ScholarPubMed
Lifschitz, A., Entrocasso, C., Alvarez, L., Lloberas, M., Ballent, M., Manazza, G., Virkel, G., Borda, B. and Lanusse, C. (2010 a). Interference with P-glycoprotein improves ivermectin activity against adult resistant nematodes in sheep. Veterinary Parasitology 172, 291–298.CrossRefGoogle ScholarPubMed
Lifschitz, A., Suarez, V. H., Sallovitz, J., Cristel, S. L., Imperiale, F., Ahoussou, S., Schiavi, C. and Lanusse, C. (2010 b). Cattle nematodes resistant to macrocyclic lactones: comparative effects of P-glycoprotein modulation on the efficacy and disposition kinetics of ivermectin and moxidectin. Experimental Parasitology 125, 172–178.CrossRefGoogle ScholarPubMed
Lin, J. H. (2003). Drug–drug interaction mediated by inhibition and induction of P-glycoprotein. Advanced Drug Delivery Reviews 55, 53–81.CrossRefGoogle ScholarPubMed
Lincke, C. R., Broecks, I. T., Plasterk, R. H. A. and Borst, P. (1993). The expression of two P-glycoprotein (pgp) genes in transgenic Caenorhabditis elegans is confined to intestinal cells. EMBO Journal 12, 1615–1620.CrossRefGoogle ScholarPubMed
McConville, M., Brennan, G. P., Flanagan, A., Hanna, R. E. B., Edgar, H. W. J., Castillo, R., Hernández-Campos, A. and Fairweather, I. (2009). Surface changes in adult Fasciola hepatica following treatment in vivo with the experimental fasciolicide, compound alpha. Parasitology Research 105, 757–767.CrossRefGoogle ScholarPubMed
Messerli, S. M., Kasinathan, R. S., Morgan, W., Spranger, S. and Greenberg, R. M. (2009). Schistosoma mansoni P-glycoprotein levels increase in response to praziquantel exposure and correlate with reduced praziquantel susceptibility. Molecular and Biochemical Parasitology 167, 54–59.CrossRefGoogle ScholarPubMed
Molento, M. B. and Prichard, R. K. (1999). Effects of the multidrug-reversing agents verapamil and CL 347,099 on the efficacy of ivermectin or moxidectin against unselected and drug-selected strains of Haemonchus contortus in jirds. Parasitology Research 85, 1007–1011.CrossRefGoogle ScholarPubMed
Molento, M. B., Lifschitz, A., Sallovitz, J., Lanusse, C. and Prichard, R. (2004). Influence of verapamil on the pharmacokinetics of the antiparasitic drugs ivermectin and moxidectin in sheep. Parasitology Research 92, 121–127.CrossRefGoogle ScholarPubMed
Mottier, L., Virkel, G., Solana, H., Alvarez, L., Salles, J. and Lanusse, C. (2004). Triclabendazole biotransformation and comparative diffusion of the parent drug and its oxidized metabolites into Fasciola hepatica. Xenobiotica 34, 1043–1057.CrossRefGoogle ScholarPubMed
Mottier, L., Alvarez, L., Ceballos, L. and Lanusse, C. (2006 a). Drug transport in helminth parasites: passive diffusion of benzimidazole anthelmintics. Experimental Parasitology 113, 49–57.CrossRefGoogle ScholarPubMed
Mottier, L., Alvarez, L., Fairweather, I. and Lanusse, C. (2006 b). Resistance-induced changes in triclabendazole transport in Fasciola hepatica: ivermectin reversal effect. Journal of Parasitology 6, 1355–1360.CrossRefGoogle Scholar
Newton, D. J., Wang, R. W. and Lu, A. Y. H. (1995). Cytochrome P450 inhibitors: evaluation of specificities in the in vitro metabolism of therapeutic agents by human liver microsomes. Drug Metabolism and Disposition 23, 154–158.Google ScholarPubMed
Nobili, S., Landini, I., Giglioni, B. and Mini, E. (2006). Pharmacological strategies for overcoming drug resistance. Current Drug Targets 7, 861–879.CrossRefGoogle Scholar
Pakharukova, M. Y., Ershov, N. I., Vorontsova, E. V., Katokhin, A. V., Merkulova, T. I. and Mordvinov, V. A. (2012). Cytochrome P450 in fluke Opisthorchis felineus: identification and characterization. Molecular and Biochemical Parasitology 181, 190–194.CrossRefGoogle ScholarPubMed
Pelkonen, O., Turpeinen, M., Hakkola, M., Honkakoski, P., Hukkanen, J. and Raunio, H. (2008). Inhibition and induction of human cytochrome P450 enzymes: current status. Archives of Toxicology 82, 667–715.CrossRefGoogle ScholarPubMed
Perez-Tomas, R. (2006). Multidrug resistance: retrospect and prospects in anti-cancer treatment. Current Medicinal Chemistry 13, 1859–1876.CrossRefGoogle Scholar
Pereira, E., Teodori, E., Dei, S., Gualtieri, F. and Garnier-Suillerot, A. (1995). Reversal of multidrug resistance by verapamil analogues. Biochemical Pharmacology 50, 451–457.CrossRefGoogle ScholarPubMed
Prichard, R. K. and Roulet, A. (2007). ABC transporters and β-tubulin in macrocyclic lactone resistance: prospects for marker development. Parasitology 134, 1123–1132.CrossRefGoogle ScholarPubMed
Reed, M. B., Panaccio, M., Strugnell, R. A. and Spithill, T. W. (1998). Developmental expression of a Fasciola hepatica sequence homologous to ABC transporters. International Journal for Parasitology 28, 1375–1381.CrossRefGoogle ScholarPubMed
Robinson, M. W., Trudgett, A., Hoey, E. M. and Fairweather, I. (2002). Triclabendazole-resistant Fasciola hepatica: ß-tubulin and response to in vitro treatment with triclabendazole. Parasitology 124, 325–338.CrossRefGoogle Scholar
Robinson, M. W., Lawson, J., Trudgett, A., Hoey, E. M. and Fairweather, I. (2004). The comparative metabolism of triclabendazole sulphoxide by triclabendazole-susceptible and triclabendazole-resistant Fasciola hepatica. Parasitology Research 92, 205–210.CrossRefGoogle ScholarPubMed
Ryan, L., Hoey, E., Trudgett, A., Fairweather, I., Fuchs, M., Robinson, M. W., Chambers, E., Timson, D. J., Ryan, E., Feltwell, T., Ivens, A., Bentley, G. and Johnston, D. (2008). Fasciola hepatica expresses multiple α- and β-tubulin isotypes. Molecular and Biochemical Parasitology 159, 73–78.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Sandstrom, R., Knutson, T. W., Knutson, L., Jansson, B. and Lennernäs, H. (1999). The effect of ketoconazole on the jejuna permeability and CYP3A metabolism of (R/S)-verapamil in humans. British Journal of Clinical Pharmacology 48, 180–189.CrossRefGoogle Scholar
Sato, H., Kusel, J. R. and Thornhill, J. (2002). Functional visualization of the excretory system of adult Schistosoma mansoni by the fluorescent marker resorufin. Parasitology 125, 527–535.CrossRefGoogle ScholarPubMed
Sato, H., Kusel, J. R. and Thornhill, J. (2004). Excretion of fluorescent substrates of mammalian multidrug resistance-associated protein (MRP) in the Schistosoma mansoni excretory system. Parasitology 128, 43–52.CrossRefGoogle ScholarPubMed
Savage, J., Meaney, M., Brennan, G. P., Hoey, E., Trudgett, A. and Fairweather, I. (2013). Effect of the P-glycoprotein inhibitor, R(+)-verapamil on the drug susceptibility of a triclabendazole-resistant isolate of Fasciola hepatica. Veterinary Parasitology 195, 72–86 doi:10.1016/j.vetpar.2013.03.07.CrossRefGoogle ScholarPubMed
Siegsmund, M. J., Cardarelli, C., Akasentjevich, I., Sugimoto, Y., Pastan, I. and Gottesman, M. M. (1994). Ketoconazole effectively reverses multidrug resistance in highly resistant KB cells. Journal of Urology 151, 485–491.CrossRefGoogle ScholarPubMed
Smith, J. M. and Prichard, R. K. (2002). Localization of P-glycoprotein mRNA in the tissues of Haemonchus contortus adult worms and its relative abundance in drug-selected and susceptible strains. Journal of Parasitology 88, 612–620.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.CrossRefGoogle ScholarPubMed
Solana, H., Scarcella, S., Virkel, G., Ceriani, C., Rodríguez, J. and Lanusse, C. (2009). Albendazole enantiometric metabolism and binding to cytosolic proteins in the liver fluke Fasciola hepatica. Veterinary Research Communications 33, 163–173.CrossRefGoogle Scholar
Stitt, L. E., Tompkins, J. B., Dooley, L. A. and Ardelli, B. F. (2011). ABC transporters influence sensitivity of Brugia malayi to moxidectin and have potential roles in drug resistance. Experimental Parasitology 129, 137–144.CrossRefGoogle ScholarPubMed
Striessnig, J., Grabner, M., Mitterdorfer, J., Hering, S., Sinnegger, J. and Glossman, H. (1998). Structural basis of drug binding to L Ca2+ channels. Trends in Pharmacological Sciences 19, 108–115.CrossRefGoogle ScholarPubMed
Tan, B., Piwnica-Worms, D. and Ratner, L. (2000). Multidrug resistance transporters and modulation. Current Opinion in Oncology 12, 450–458.CrossRefGoogle ScholarPubMed
Tiberghien, F. and Loor, F. (1996). Ranking of P-glycoprotein substrates and inhibitors by a calcein-AM fluorometry screening assay. Anti-Cancer Drugs 7, 568–578.CrossRefGoogle ScholarPubMed
Toffoli, G., Simone, F., Corona, G., Raschack, M., Cappelletto, B., Gigante, M. and Boiocchi, M. (1995). Structure–activity relationship of verapamil analogs and reversal of multidrug resistance. Biochemical Pharmacology 50, 1245–1255.CrossRefGoogle ScholarPubMed
Tompkins, J. B., Stitt, L. E., Morrissette, A. M. and Ardelli, B. F. (2011). The role of Brugia malayi ATP-binding cassette (ABC) transporters in potentiating drug sensitivity. Parasitology Research 109, 1311–1322.CrossRefGoogle ScholarPubMed
Toner, E., McConvery, F., Brennan, G. P., Meaney, M. and Fairweather, I. (2009). A scanning electron microscope study on the route of entry of triclabendazole into the liver fluke, Fasciola hepatica. Parasitology 136, 523–535.CrossRefGoogle Scholar
Toner, E., Brennan, G. P., McConvery, F., Meaney, M. and Fairweather, I. (2010). A transmission electron microscope study on the route of entry of triclabendazole into the liver fluke, Fasciola hepatica. Parasitology 137, 855–870.CrossRefGoogle Scholar
Triggle, D. J. (2006). L-type calcium channels. Current Pharmaceutical Design 12, 443–457.CrossRefGoogle ScholarPubMed
Varma, M. V. S., Ashkraj, Y., Dey, C. S. and Panchagnula, R. (2003). P-glycoprotein inhibitors and their screening: a perspective from bioavailability enhancement. Pharmacological Research 48, 347–359.CrossRefGoogle ScholarPubMed
Virkel, G., Lifschitz, A., Sallovitz, J., Ballent, M., Scarcella, S. and Lanusse, C. (2009). Inhibition of cytochrome P450 activity enhances the systemic availability of triclabendazole metabolites in sheep. Journal of Veterinary Pharmacology and Therapeutics 32, 79–86.CrossRefGoogle ScholarPubMed
Walker, S. M., McKinstry, B., Boray, J. C., Brennan, G. P., Trudgett, A., Hoey, E. M., Fletcher, H. and Fairweather, I. (2004). Response of two isolates of Fasciola hepatica to treatment with triclabendazole in vivo and in vitro. Parasitology Research 94, 427–438.CrossRefGoogle ScholarPubMed
Wang, E.-J., Lew, K., Casciano, N., Clement, R. P. and Johnson, W. W. (2002). Interaction of common azole antifungals with P glycoprotein. Antimicrobial Agents and Chemotherapy 46, 160–165.CrossRefGoogle ScholarPubMed
Ward, K. W., Stelman, G. J., Morgan, J. A., Zeigler, K. S., Azzarano, L. M., Kehler, J. R., McSurdy-Freed, J. E., Proksch, J. W. and Smith, B. R. (2004). Development of an in vivo preclinical screen model to estimate absorption and first-pass hepatic extraction of xenobiotics. II. Use of ketoconazole to identify P-glycoprotein/CYP3A-limited bioavailability in the monkey. Drug Metabolism and Disposition 32, 172–177.CrossRefGoogle Scholar
Wilkinson, R., Law, C. J., Hoey, E. M., Fairweather, I., Brennan, G. P. and Trudgett, A. (2012). An amino acid substitution in Fasciola hepatica P-glycoprotein from triclabendazole-resistant and triclabendazole-susceptible populations. Molecular and Biochemical Parasitology 186, 69–72.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Xu, M., Molento, M., Blackhall, W., Riberio, P., Beech, R. and Prichard, R. (1998). Ivermectin resistance in nematodes may be caused by alteration of P-glycoprotein homolog. Molecular and Biochemical Parasitology 91, 327–335.CrossRefGoogle ScholarPubMed
Yan, R., Urdaneta-Marquez, L., Keller, K., James, C. E., Davey, M. W. and Prichard, R. K. (2012). The role of several ABC transporter genes in ivermectin resistance in Caenorhabditis elegans. Veterinary Parasitology 190, 519–529.CrossRefGoogle ScholarPubMed
Ye, Z. G. and Van Dyke, K. (1988). Reversal of chloroquine resistance in falciparum malaria independent of calcium channels. Biochemical and Biophysical Research Communications 30, 476–481.Google Scholar
Zhang, Y., Hsieh, Y., Izumi, T., Lin, E. T. and Benet, L. Z. (1998). Effects of ketoconazole on the intestinal metabolism, transport and oral bioavailability of K02, a novel vinylsulfone peptidomimetic cysteine protease inhibitor and a P450 3A, P-glycoprotein dual substrate, in male Sprague–Dawley rats. Journal of Pharmacology and Experimental Therapeutics 287, 246–252.Google Scholar
Zhao, Z., Sheps, J. A., Ling, V., Fang, L. L. and Baillie, D. L. (2004). Expression analysis of ABC transporters reveals differential functions of tandemly duplicated genes in Caenorhabditis elegans. Journal of Molecular Biology 344, 409–417.CrossRefGoogle ScholarPubMed