Activity Of Mu And Pi Glutathione S-Transferase Isoenzymes In Fasciola hepatica Triclabendazole Susceptible And Resistant Strains

FERNÁNDEZ V.; CADENAZZI G.; ORTIZ OBRITAS P.; SOLANA M.; SANSINANEA A.; SOLANA H.

JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2012 vol. 35 p. 129 - 129

0140-7783

Fasciolosis produced by the trematode Fasciola hepatica is an economically important disease of livestock which is controlled by the anthelmintic triclabendazole. Triclabendazole (TCBZ) ismetabolized into its active sulphoxide metabolite (TCBZSO) by the host liver but also by the parasite. Resistance to TCBZ is associated with an enhanced metabolic activity carried on by amultienzymatic action involving more than one metabolic pathway as demonstrated in our laboratory (1). Glutathione S-transferase (GST) enzymes are involved in the detoxificationof endogenous and xenobiotic compounds through glutathione conjugation or glutathione peroxidase activity and different GST-isoenzymes may have different metabolic activity. In thepresent work we evaluated the cytosolic activity of total GST, GST-mu and GST-pi-isoenzymes in TCBZ-susceptible (Cullompton) and TCBZ-resistant (Sligo and Oberon) adult Fasciola hepatica strains. Nine parasite-free Corriedale weaned lambs were each orally infected with 200 metacercariae of Fasciola hepatica, three with the Cullompton strain, three with the Sligo strain and three with the Oberon strain. Sixteen weeks after the infection, the flukes were collected and processed to obtain the cytosolic fractions (2), and the GST activity was determined as described elsewhere (3).The total GST activity (n = 5) in Sligo (1277 ± 32 nmol min)1 mg)1 protein) and Oberon (1216 ± 16 nmol min)1 mg)1 protein) resistant strains was 59% and 52% respectively higher (P < 0.001) than in the Cullompton susceptible strain (800 ± 60 nmol min)1 mg)1 protein). While GST-pi activity (substrate: Ethacrynic acid) did not differ between the different strains tested, the GST-mu activity (substrate: DCNB) in Oberon and Sligo resistant strains was 17% and 26% respectivelyhigher than in the Cullompton susceptible strain,confirming its responsability in the expression of the highest metabolic activity of total GST. This higher GST activity has potential relevance as it might contribute to the phenomenon of resistance to TCBZ. These results contribute to the understanding of the metabolic pathway and the mechanism of resistance to TCBZ in Fasciola hepatica.