Curcumin-PVP improves the in vitro efficacy of ivermectin against resistant and susceptible Haemonchus contortus

Abstract

Ivermectin (IVM) resistance in parasitic nematodes such as Haemonchus contortus has spurred a search for substances that help to recover its efficacy. One potential agent is the natural product curcumin (CUR). In this study, CUR was combined with polyvinylpyrrolidone (PVP) (CUR/PVP) to improve its solubility and biological applicability. This study determined the effect of CUR preincubation on the effective concentration 50% (EC₅₀) of IVM in three H. contortus isolates with different susceptibilities to IVM. The IVM EC₅₀ was determined for three H. contortus isolates with different IVM susceptibilities using the larval migration inhibition (LMI) test. The three isolates were (i) PARAISO (IVM resistant), (ii) FMVZ-UADY (IVM susceptible), and (iii) CENID-SAI INIFAP (reference IVM susceptible). The L₃ of each isolate were preincubated for 3 h with one of three concentrations of CUR (μg curcumin/mL): CONC-1 (3.67), CONC-2 (5.67), or CONC-3 (8.48). Corresponding controls were performed without CUR. The EC₅₀ of IVM was determined for each isolate after they were exposed to the different CUR concentrations. The EC₅₀ of IVM differed between the isolates PARAISO > FMVZ-UADY > CENID-SAI INIFAP (P < 0.05). The CUR preincubation at CONC-1 did not decrease the EC₅₀ of IVM for any of the three isolates, suggesting a hormetic effect. By contrast, CUR preincubation at CONC-2 or CONC-3 decreased the IVM EC₅₀ for the PARAISO isolate (P < 0.05) compared with the reference isolate and reduced the EC₅₀ of IVM for the FMVZ-UADY and CENID-SAI INIFAP isolates below the EC₅₀ for the CENID-SAI INIFAP isolate without CUR preincubation. In conclusion, preincubation of H. contortus L₃ with CUR reduced the EC₅₀ of IVM for field isolates classified as resistant and susceptible to IVM. The CUR preincubation reduced the IVM resistance factor in the different isolates tested.