{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:12:07Z","timestamp":1791414727359,"version":"4.3.3"},"reference-count":52,"publisher":"Cambridge University Press (CUP)","issue":"4","license":[{"start":{"date-parts":[[2005,6,16]],"date-time":"2005-06-16T00:00:00Z","timestamp":1118880000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Parasitology"],"published-print":{"date-parts":[[2005,10]]},"abstract":"<jats:p>Triclabendazole (TCBZ) is a halogenated benzimidazole compound that possesses high activity against immature and adult stages of the liver fluke, <jats:italic>Fasciola hepatica<\/jats:italic>. The intensive use of TCBZ in endemic areas of fascioliasis has resulted in the development of liver flukes resistant to this compound. TCBZ sulphoxide (TCBZSO) and TCBZ sulphone (TCBZSO<jats:sub>2<\/jats:sub>) are the main molecules recovered in the bloodstream of TCBZ-treated animals. In order to gain some insight into the possible mechanisms of resistance to TCBZ, the goals of the work described here were: to compare the <jats:italic>ex vivo<\/jats:italic> transtegumental diffusion of TCBZ parent drug and its sulpho-metabolites (TCBZSO and TCBZSO<jats:sub>2<\/jats:sub>) into TCBZ-susceptible and -resistant liver flukes; and to assess the comparative pattern of TCBZ biotransformation by TCBZ-susceptible and -resistant <jats:italic>F. hepatica<\/jats:italic>. For the tegumental diffusion studies, TCBZ-susceptible (Cullompton) and -resistant (Sligo) adult flukes collected from untreated infected sheep were incubated (15\u2013180 min) in KRT buffer containing either TCBZ, TCBZSO or TCBZSO<jats:sub>2<\/jats:sub> (5 nmol.ml<jats:sup>\u22121<\/jats:sup>). For the metabolism studies, microsomal fractions obtained from TCBZ-susceptible and -resistant flukes were incubated for 60 min with TCBZ (40 \u03bcM), and the amount of the formed metabolic product (TCBZSO) was measured. Drug\/metabolite concentrations were quantified by HPLC. All the assayed TCBZ-related molecules penetrated through the tegument of both TCBZ-susceptible and -resistant flukes. However, significantly lower (approximately 50%) concentrations of TCBZ and TCBZSO were recovered within the TCBZ-resistant flukes compared to the TCBZ-susceptible ones over the 180 min incubation period. The rate of TCBZ sulphoxidative metabolism into TCBZSO was significantly higher (39%) in TCBZ-resistant flukes. The flavin-monooxigenase (FMO) enzyme system appears to be the main metabolic pathway involved in the formation of TCBZSO in both TCBZ-susceptible and -resistant flukes. The altered drug influx\/efflux and enhanced metabolic capacity identified in TCBZ-resistant liver flukes may account for the development of resistance to TCBZ.<\/jats:p>","DOI":"10.1017\/s0031182005007997","type":"journal-article","created":{"date-parts":[[2005,6,16]],"date-time":"2005-06-16T13:28:38Z","timestamp":1118928518000},"page":"501-510","source":"Crossref","is-referenced-by-count":84,"title":["Altered drug influx\/efflux and enhanced metabolic activity in triclabendazole-resistant liver flukes"],"prefix":"10.1017","volume":"131","author":[{"given":"L. I.","family":"ALVAREZ","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. D.","family":"SOLANA","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. L.","family":"MOTTIER","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. 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(2004 b).Triclabendazole biotransformation and comparative diffusion of the parent drug and its oxidised metabolites into Fasciola hepatica .Xenobiotica 34,1043\u20131057.","DOI":"10.1080\/00498250400015285"},{"key":"S0031182005007997_ref042","doi-asserted-by":"publisher","DOI":"10.1016\/0020-7519(95)00113-1"},{"key":"S0031182005007997_ref029","doi-asserted-by":"crossref","unstructured":"Lubega, G. W. and Prichard, R. K. (1991 c).Interaction of benzimidazoles anthelmintics with Haemonchus contortus: binding affinity and anthelmintic efficacy.Experimental Parasitology 73,203\u2013213.","DOI":"10.1016\/0014-4894(91)90023-P"},{"key":"S0031182005007997_ref040","doi-asserted-by":"publisher","DOI":"10.1017\/S003118200100124X"},{"key":"S0031182005007997_ref031","doi-asserted-by":"publisher","DOI":"10.2307\/3282805"},{"key":"S0031182005007997_ref045","unstructured":"Soulsby, E. (1987). 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