In vitro evaluation of the inhibitory potential of the chiral pesticide etofumesate on the main cytochrome P450 enzymes involved in drug metabolism

• Grant number: 19/12149-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2019
• End date: March 31, 2020
• Field of knowledge: Health Sciences - Pharmacy - Toxicological Analysis
• Principal Investigator: Anderson Rodrigo Moraes de Oliveira
• Grantee: Jade Lorena Mariano Bucci
• Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Ethofumesate (ETO) is a pesticide of the class of benzofuranil herbicides widely used in beet, sprout and grass crops. The ETO has a center of asymmetry, in other words, exist as a pair of enantiomers. Studies have shown that pesticides can inhibit the cytochrome P450 (CYP450) enzymes, which are responsible for the metabolism of approximately 70% of the drugs marketed; in addition, some studies have found that the CYP450 inhibition occurred enantioselectively. Due to the presence of pesticide residues in the in water and food samples, and the scarcity of reports regarding the consequences of the interactions between pesticides and the human organism, this project proposes to evaluate whether the chiral pesticide ETO is able to inhibit, in vitro, the major CYP450 enzymes involved in drug metabolism (CYP1A2, CYP2B6, CYP2D6, CYP2C9, CYP2C19, CYP2E1 and CYP3A4/5) to further to predict pesticide-drug interaction. It is known that enantiomers may selectively interact in organisms, due to this, the enzymatic inhibition with the isolated enantiomers will be investigated to evaluate if there is difference in the inhibitory potential between them and also in comparison to the racemic mixture. The risk assessment for pesticides in this study is of great importance since the inhibition of cytochrome P450 enzymes may alter the pharmacokinetics of a particular drug causing a possible intoxication.

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)

PEROVANI, ICARO SALGADO; MARIANO BUCCI, JADE LORENA; CARRAO, DANIEL BLASCKE; SANTOS BARBETTA, MAIKE FELIPE; DA SILVA, RODRIGO MOREIRA; LOPES, NORBERTO PEPORINE; MORAES DE OLIVEIRA, ANDERSON RODRIGO. Enantioselective inhibition of human CYP2C19 by the chiral pesticide ethofumesate: Prediction of pesticide-drug interactions in humans. Chemico-Biological Interactions, v. 345, AUG 25 2021. (14/50945-4, 18/07534-4, 19/12149-5, 20/02139-0)