Triclabendazole (TCBZ) and albendazole (ABZ) are flukicidal benzimidazole compounds extensively used in veterinary medicine. Although TCBZ has excellent activity against mature and immature stages of the liver fluke, Fasciola hepatica, ABZ action is restricted to flukes older than 12 wk. The intensive use of TCBZ has resulted in the development of resistance. To gain insight into the mechanisms of resistance to TCBZ, the ex vivo diffusion of TCBZ, TCBZ sulfoxide (TCBZSO, the active metabolite of TCBZ), and ABZ into TCBZ-susceptible and -resistant adult flukes was compared. TCBZ-susceptible (Cullompton) and -resistant (Sligo) flukes were incubated in Krebs-Ringer Tris buffer with either TCBZ, TCBZSO, or ABZ (5 nmol/ ml) for 90 min. Drug/metabolite concentrations were quantified by high-performance liquid chromatography. All the assayed molecules penetrated through the tegument of both susceptible and resistant flukes. However, significantly lower concentrations of TCBZ and TCBZSO were recovered within the TCBZ-resistant flukes. In contrast, ABZ entrance into the susceptible and resistant flukes was equivalent. The influx/efflux balance for TCBZ, TCBZSO, and ABZ in susceptible and resistant flukes in the presence or absence of a substrate (ivermectin) of the drug transporter P-glycoprotein was assessed. The ivermectin-induced modulation of P-glycoprotein activity decreased TCBZ efflux from the resistant flukes. Higher concentrations of TCBZ and TCBZSO were recovered from the resistant liver flukes in the presence of ivermectin. Thus, an altered influx/efflux mechanism may account for the development of resistance to TCBZ in F. hepatica.
Skip Nav Destination
Article navigation
December 2006
Research Article|
December 01 2006
RESISTANCE-INDUCED CHANGES IN TRICLABENDAZOLE TRANSPORT IN FASCIOLA HEPATICA: IVERMECTIN REVERSAL EFFECT
L. Mottier
;
L. Mottier
Laboratorio de Farmacología, Departamento de Fisiopatología, Facultad de Ciencias Veterinarias, Universidad Nacional del Centro de la Provincia de Buenos Aires (UNCPBA), Campus Universitario, 7000, Tandil, Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina. clanusse@vet.unicen.edu.ar
Search for other works by this author on:
L. Alvarez
;
L. Alvarez
Laboratorio de Farmacología, Departamento de Fisiopatología, Facultad de Ciencias Veterinarias, Universidad Nacional del Centro de la Provincia de Buenos Aires (UNCPBA), Campus Universitario, 7000, Tandil, Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina. clanusse@vet.unicen.edu.ar
Search for other works by this author on:
I. Fairweather
;
I. Fairweather
Laboratorio de Farmacología, Departamento de Fisiopatología, Facultad de Ciencias Veterinarias, Universidad Nacional del Centro de la Provincia de Buenos Aires (UNCPBA), Campus Universitario, 7000, Tandil, Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina. clanusse@vet.unicen.edu.ar
* Parasite Proteomics and Therapeutics Research Group, School of Biology and Biochemistry, The Queen's University of Belfast, Medical Biology Centre, Belfast BT9 7BL, U.K
Search for other works by this author on:
C. Lanusse
C. Lanusse
Laboratorio de Farmacología, Departamento de Fisiopatología, Facultad de Ciencias Veterinarias, Universidad Nacional del Centro de la Provincia de Buenos Aires (UNCPBA), Campus Universitario, 7000, Tandil, Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina. clanusse@vet.unicen.edu.ar
† To whom correspondence should be addressed
Search for other works by this author on:
J Parasitol (2006) 92 (6): 1355–1360.
Citation
L. Mottier, L. Alvarez, I. Fairweather, C. Lanusse; RESISTANCE-INDUCED CHANGES IN TRICLABENDAZOLE TRANSPORT IN FASCIOLA HEPATICA: IVERMECTIN REVERSAL EFFECT. J Parasitol 1 December 2006; 92 (6): 1355–1360. doi: https://doi.org/10.1645/GE-922R.1
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Sign in via your Institution
Sign in via your InstitutionCiting articles via
PRELIMINARY EXPERIMENTATIONS ON THE IN VITRO REARING OF HEMATOPHAGOUS PIGEON LOUSE HOHORSTIELLA LATA (AMBLYCERA: PHTHIRAPTERA: INSECTA)
Ghazi Khan, Shalini Roy, Nidhi Gupta, Aftab Ahmad, Surendra Kumar
REVIEW OF PARASITES FOUND IN EXTINCT ANIMALS: WHAT CAN BE REVEALED
Paula Cascardo, Elisa Pucu, Daniela Leles
THE EFFICACY OF MARINE NATURAL PRODUCTS AGAINST PLASMODIUM FALCIPARUM
Yukihiro Goto, Rie Kamihira, Yoichi Nakao, Motohiro Nonaka, Ryo Takano, Xuenan Xuan, Kentaro Kato
MORPHOLOGICAL AND MOLECULAR CHARACTERIZATION OF THE PLAGUE VECTOR XENOPSYLLA BRASILIENSIS
Saeed Mohammadi, Heike Lutermann, Sasha Hoffmann, Arsalan Emami-Khoyi, Heather J. Webster, Dina Fagir, Nigel C. Bennett, Bettine Jansen van Vuuren
MOLECULAR INVESTIGATION AND PHYLOGENETIC ANALYSIS OF ANAPLASMOSIS IN DOGS
Hammad Nayyar Ghauri, Muhammad Ijaz, Arslan Ahmed, Muhammad Umair Aziz Muhammad Naveed, Yasir Nawab, Muhammad Umar Javed, Awais Ghaffar