Interaction of essential oils and phenolic compounds as P-glycoprotein inhibitors (Ivermectin resistance factor) in Haemonchus contortus through in vitro tests and PCR-Real Time.

• Grant number: 17/23540-1
• Support Opportunities: Regular Research Grants
• Duration: May 01, 2018 - July 31, 2020
• Field of knowledge: Agronomical Sciences - Animal Husbandry - Animal Production
• Principal Investigator: Luciana Morita Katiki
• Grantee: Luciana Morita Katiki
• Host Institution: Instituto de Zootecnia. Agência Paulista de Tecnologia dos Agronegócios (APTA). Secretaria de Agricultura e Abastecimento (São Paulo - Estado). Nova Odessa , SP, Brazil
• Associated researchers: Alessandro Francisco Talamini Do Amarante ; Cecília José Veríssimo ; Helder Louvandini ; Patricia Louvandini
• Associated scholarship(s): 18/15206-7 - Interaction of essential oils and phenolic compounds as P-glycoprotein modulators evaluated in Haemonchus contortus resistant strain., BP.TT

Abstract

Ivermectin is an endectocidal drug widely used to control gastrointestinal nematode infections. However, due to its wide and incorrect use, there was a process of selection of parasites resistant to the molecule. The gastrointestinal nematode of sheep, Haemonchus contortus has been resistant to ivermectin in many national and international reports. Although the presence of ineffectiveness has been verified, ivermectin is a widely sold product because the molecule have strong commercial diffusion due to its excellent action when it was launched. Some mechanisms of resistance to ivermectin were described, however, the activity of P-glycoprotein (P-GP) is discussed as the main reason for the development of resistance. The use of phytochemicals in drug formulations may increase their efficacy by improving pharmacokinetics, improving anthelmintic activity with reduced doses and reducing adverse effects. It is known that some essential oils and also some phenolic compounds have the capacity to inhibit the transport activity of P-GP and therefore, could present a decrease in the activity of the mechanisms of resistance to ivermectin. The identification of an effective P-GP modulator among phytochemical compounds has the advantage of being safer and less toxic when compared to verapamil and cyclosporin (usual P-GP inhibitors). The objective of this work is to evaluate the antihelmintic activity of ivermectin under H. contortus resistant and sensitive strain alone and the potential activity of essential oils and phenolic compounds on the mechanisms of resistance of the parasite in motility test of H. contortus in vitro. The anthelmintic activity will be evaluated by comparing LC50 of each association between (ivermectin + phytochemicals). The level of G-glycoprotein expression will be assessed using the Quantitative Real-Time PCR technique. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PACHECO, POLIANA ARAUJO; LOUVANDINI, HELDER; GIGLIOTI, RODRIGO; RODRIGUES WEDY, BRUNA COSTA; RIBEIRO, JESSICA CAROLINA; VERISSIMO, CECILIA JOSE; FERREIRA, JORGE FREIRE DA SILVA; TALAMINI DO AMARANTE, ALESSANDRO FRANCISCO; KATIKI, LUCIANA MORITA. Phytochemical modulation of P-Glycoprotein and its gene expression in an ivermectin-resistant Haemonchus contortus isolate in vitro. Veterinary Parasitology, v. 305, p. 9-pg., 2022-05-01. (17/23540-1, 18/02423-0, 18/19452-2, 18/15206-7)