کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5803087 | 1555680 | 2014 | 8 صفحه PDF | دانلود رایگان |
- Eight P-gp modulating drugs were associated to ivermectin in vitro.
- Cyclosporin A caused the highest reduction in IVM EC50.
- The effect of P-gp modulating drugs depends of ivermectin concentration.
- The modulator drugs increased ivermectin efficacy against Haemonchus placei.
Since its production in the 1980s, ivermectin (IVM) has been used indiscriminately and the selection pressure to which bovine gastrointestinal nematodes have been exposed has been intense, resulting in considerable economic losses due to parasitic resistance. One possibility for the control of resistant parasites is the use of P-glycoprotein (P-gp) modulators, because one of the main biochemical changes in ivermectin-resistant parasites is the increased activity of membrane proteins responsible for the efflux of drugs and xenobiotics. This study aimed to evaluate the in vitro effect of eight P-gp modulating drugs to potentiate IVM efficacy against an IVM-resistant field isolate of Haemonchus placei (Nematoda: Trichostrongylidae). The association of IVM with cyclosporin-A, ceftriaxone, dexamethasone, diminazene aceturate, quercetin, trifluoperazine, verapamil, or vinblastine resulted in increased IVM (10â4Â M) efficacy of 5.1%, 49.06%, 76.42%, 3.31%, 28.85%, 13.74%, 45.64% and 43.61%, respectively, and reduced the IVM half maximal effective concentration (EC50) from 4.381Â ÃÂ 10â6Â M to 9.877Â ÃÂ 10â8, 2.739Â ÃÂ 10â7, 1.240Â ÃÂ 10â6, 1.651Â ÃÂ 10â6, 2.710Â ÃÂ 10â7, 1.159Â ÃÂ 10â7, 1.026Â ÃÂ 10â6 and 7.136Â ÃÂ 10â7Â M, respectively. Only diminazene aceturate did not significantly reduce the number of migrating larvae when associated with IVM (PÂ >Â 0.05). The effect of P-gp modulating drugs depended on IVM concentration, with greater potentiating effect at lower IVM concentrations. The in vitro application of trifluoperazine, dexamethasone, quercetin, verapamil, cyclosporin A, vinblastine, and ceftriaxone potentiated IVM efficacy against an IVM-resistant field isolate of H. placei, resulting in higher efficacy and lower IVM EC50.
Journal: Veterinary Parasitology - Volume 205, Issues 3â4, 15 October 2014, Pages 638-645