Increase anthelmintic activity of Ivermectin by synergistic action of phytochemical compounds in Haemonchus contortus

• Grant number: 18/02423-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): May 01, 2018
• Effective date (End): August 31, 2021
• Field of knowledge: Agronomical Sciences - Veterinary Medicine
• Principal Investigator: Helder Louvandini
• Grantee: Poliana Araújo Pacheco
• Host Institution: Centro de Energia Nuclear na Agricultura (CENA). Universidade de São Paulo (USP). Piracicaba , SP, Brazil

Abstract

The gastrointestinal nematode of sheep, Haemonchus contortus has been resistant to several active principles, among them Ivermectin, anthelmintic with antihelminthic resistance, but widely used for the treatment and control of gastrointestinal nematodes in sheep. Some mechanisms of resistance to ivermectin have been elucidated and the participation of the P-glycoprotein is listed as the main involved in the development of the resistance. The use of combinations between medicinal products and phytochemical compounds and / or essential oils has demonstrated promising possibilities of potentiation of pharmacological activity while reducing doses and adverse effects. Essential oils and phenolic compounds may act as modulators of P-glycoprotein activity. Identification of an effective modulator among phytochemical compounds would be an alternative to the use of other known toxic inhibitors such as verapamil and cyclosporin. The objective of this work is to evaluate and compare the antihelmintic activity of Ivermectin under H. contortus strain resistant and sensitive alone, and to verify the action potential of essential oils and phytochemical compounds associated with Ivermectin on the resistance mechanisms of the parasite through tests in vitro. The anthelmintic activity will be evaluated by comparing the LC50 of each combination: Ivermectin + phytochemical compounds. The level of P-glycoprotein expression to be observed from the most promising Ivermectin / Phytochemical Compounds in resistant H. contortus strain will be evaluated using the Quantitative Real-Time PCR technique.