IDENTIFICATION AND DIFFERENTIAL ACTIVITY OF GLUTATHIONE S-TRANSFERASE MU IN STRAINS OF FASCIOLA HEPATICA SUSCEPTIBLE AND RESISTANT TO TRICLABENDAZOLE

FERNANDEZ VANESA.

Amino Acid - New Insights and Roles in Plant and Animal

intechopen.

Año: 2017; p. 1 - 292

Fasciolahepatica is a helminth parasite that causes fascioliasis in domestic ruminants and humans. Economic losses due to its infection are estimated in US$ 2000?3000 million yearly . The anthelmintics are at present the only weapon against these parasitic helminths . The parasite resistance to different anthelmintics including that of F. hepatica to triclabendazole (TCBZ) is growing worldwide. Glutathione S‐transferases (GSTs) are enzymes involved in the detoxification of a wide range of substrates through chemical conjugation with glutathione, so that the product becomes more soluble in water, less toxic and easier to excrete. Eight GST isoenzymes are present in F. hepatica. Since the different isoenzymes do not necessarily have the same metabolic activity, in the present work, we evaluated the metabolic activity of total cytosolic GST and GST mu and GST pi isoenzymes in adult strains of F. hepatica susceptible (Cullompton) and resistant (Sligo and Oberon) to TCBZ of the highest metabolic activity of total GST. The genetic sequence database at the National Center for Biotechnical Information (NCBI) (GenBank ID: KF680281?KF680282) corresponding to the GST mu gene isolated from Cullompton strain (TCBZ‐susceptible) and (GenBank ID: KF680283?KF680284) corresponding to the GST mu gene isolated from Sligo strain (TCBZ‐resistant) in F. hepatica. Comparative analysis of both strains, Cullompton and Sligo, showed two nucleotide changes and change of one amino acid in the GST mu isoenzyme of the TCBZ‐resistant strain. These results together with the higher enzymatic activity of GST have a potential relevance as it contribute to the understanding the mechanisms that generate resistance to anthelmintics and the activity, metabolism, and disposition of these drugs in the parasite