Monoterpenes as potential tools to improve the activity of synthetic anthelmintics: pharmacological screening of their effects on drug metabolism and intestinal accumulation

MIRÓ, MARÍA VICTORIA; COSTA-JÚNIOR, LIVIO ; ALVAREZ, LUIS IGNACIO; LANUSSE, CARLOS EDMUNDO; VIRKEL, GUILLERMO LEÓN; LIFSCHITZ, ADRIAN LUIS

Dublin

Congreso; 28º Conference of the World Association for the Advancement of Veterinary Parasitology WAAVP; 2021

The search for novel alternaves to control gastrointesnal nematodes in ruminants is relevant considering the increasing of anthelminc resistance. The use of monoterpenes may contribute to improving parasite control by enhancing the effecveness of exisng synthec anthelminc drugs. The work described here evaluated in vitro the effects of monoterpenes on the processes of drug metabolism and intesnal accumulaon and addionally, the anthelminc acvity of the best ?candidate?. In Trial 1 the intesnal accumulaon of Rhodamine123 (Rho123), a P-glycoprotein substrate, was studied in cale ileum in the presence or absence of carvone (CNE), geraniol (GNL), citral (CTL), anethole (ANT), carvacrol (CVC) and thymol (TML). The effect of CNE, GNL and CTL on flavin-containing monooxygenase (FMO) and cytochrome P450 (CYP) dependent metabolism was assessed in sheep liver microsomes measuring specific enzyme acvies. Among the monoterpenes tested, only the presence of CNE and GNL increased the accumulaon of Rho123 by 73 % and 44 % respecvely (P