Risk assessment of the chiral pesticide prothioconazole in human models: in vitro-in vivo correlation, prediction of drug-pesticide interaction and cyto- and genotoxicity studies

• Grant number: 20/02139-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: June 01, 2020
• End date: August 31, 2024
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Analytical Chemistry
• Principal Investigator: Anderson Rodrigo Moraes de Oliveira
• Grantee: Icaro Salgado Perovani
• Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 22/00127-0 - A microfluidic device for inhibition studies with human cytochrome P450 enzymes, BE.EP.DR

Abstract

Worldwide, the pesticides use has been significantly increasing. Hence, non-target organisms, such as humans, may be more exposed to its toxic effects. Prothioconazole is a fungicide used in Brazil, the United States of America and European Union countries in cotton, barley, corn and wheat crops. Since it is a chiral fungicide, each enantiomer may interact differently in chiral environments, such as organisms' biomolecules, which leads to enantioselective behavior. Some studies have demonstrated the prothioconazole enantioselective behavior in different environments, this represents indication that its metabolism in the human organism may be enantioselective. In this sense, the goal of this research project will be to perform a wide study with different human models aiming further risk assessment of the pesticide. For this purpose, the enantioselective metabolism of prothioconazole will be performed using human liver microsomes and further in vitro-in vivo correlation to determine the toxicokinetic parameters (i) hepatic clearance; (ii) hepatic extraction ratio and (iii) bioavailable fraction of the fungicide. Reaction phenotyping and inhibition studies of the main cytochrome P450 (CYP450) isoforms responsible for drug metabolism will be performed for assessment of drug-pesticide interactions. At last, cyto- and genotoxicity enantioselective studies will be performed to evaluate if the pesticide may present enantioselective toxicity to human cells. The studies will be conducted with the racemic mixture and the isolated enantiomers to compare the results. (AU)

Scientific publications

(4)

(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; SERPELLONE, CAROLINA OLIVEIRA; DE OLIVEIRA, ANDERSON RODRIGO MORAES. An appraisal of experimental designs: Application to enantioselective capillary electromigration techniques. ELECTROPHORESIS, v. 42, n. 17-18, SI, p. 1726-1743, SEP 2021. (14/50945-4, 18/07534-4, 20/02139-0)

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)

PEROVANI, ICARO SALGADO; SANTOS BARBETTA, MAIKE FELIPE; DA SILVA, RODRIGO MOREIRA; LOPES, NORBERTO PEPORINE; MORAES DE OLIVEIRA, ANDERSON RODRIGO. In vitro-in vivo correlation of the chiral pesticide prothioconazole after interaction with human CYP450 enzymes. Food and Chemical Toxicology, v. 163, p. 8-pg., 2022-03-22. (21/10098-4, 20/02139-0, 14/50945-4)

PEROVANI, ICARO SALGADO; SERPELLONE, CAROLINA OLIVEIRA; DE OLIVEIRA, ANDERSON RODRIGO MORAES. An appraisal of experimental designs: Application to enantioselective capillary electromigration techniques. ELECTROPHORESIS, FEB 2021. (18/07534-4, 14/50945-4, 20/02139-0)