MONOTERPENES AS POTENTIAL TOOLS TO IMPROVE THE ACTIVITY OF SYNTHETIC ANTHELMINTICS: PHARMACOLOGICAL SCREENING OF THEIR EFFECTS ON DRUG METABOLISM AND INTESTINAL ACCUMULATION

MIRÓ, M.V.; COSTA-JUNIOR, L.M.; ALVAREZ, L.; LANUSSE, C.; VIRKEL, G.L.; LIFSCHITZ, A.L.

DUBLIN

Congreso; 28th International Conference of the World Association for the Advancement of Veterinary Parasitology; 2021

The search for novel alternatives to control gastrointestinal nematodes in ruminants is relevant considering the increasing of anthelmintic resistance. The use of monoterpenes may contribute to improving parasite control by enhancing the effectiveness of existing synthetic anthelmintic drugs. The work described here evaluated in vitro the effects of monoterpenes on the processes of drug metabolism and intestinal accumulation and additionally, the anthelmintic activity of the best ?candidate?. In Trial 1 the internal accumulation of Rhodamine- 123 (Rho123), a P-glycoprotein substrate, was studied in cattle 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 activities. Among the monoterpenes tested, only the presence of CNE and GNL increased the accumulation of Rho123 by 73 % and 44 % respectively (P