Enhanced albendazole sulphoxidative metabolism in triclabendazole-resistant liver flukes

SOLNA H, VIRKEL G, RODRIGUEZ J,CERIANI C, MOTTIER L, ALVAREZ L, LANUSSE C.

JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS

Blackwell Synergy

Año: 2006 vol. 29 p. 123 - 123

0140-7783

Fasciola hepatica is a cosmopolitan trematode parasite which causes considerable losses in livestock all over the world. Triclabendazole (TCBZ) is a halogenated benzimidazole compound highly effective against both juvenile and adult F. hepatica (1). The ability of different helminths to biotransform xenobiotic compounds has been demonstrated (2, 3). We have previously shown that both the microsomal and cytosolic fractions of F. hepatica oxidize the sulphur-containing flukicidal benzimidazole anthelmintics, albendazole (ABZ) (3) and TCBZ (4).  The intensive use of TCBZ in endemic areas of fascioliasis has resulted in the emergence of resistant liver flukes. Recent work addressed to identify the mechanisms of resistance to TCBZ indicated that the transtegumental influx/efflux balance for TCBZ and its main metabolites is altered in resistant (R) flukes, which accounted for a reduced amount of active drug being recovered within the R compared to the susceptible (S) parasite (5). Furthermore, a higher capacity to oxidize TCBZ into its sulphoxide metabolite (TCBZO) was observed in R flukes compared with the S strain of the trematode parasite. The assays described here were performed to assess the potential involvement of an altered metabolism as a resistance mechanism towards TCBZ chemically-related compounds. This complementary work was addressed to characterize the pattern of ABZ microsomal sulphoxidation in TCBZ-susceptible (TCBZ-S) and TCBZ-resistant (TCBZ-R) strains of F. hepatica