Enantioselective in vitro studies of metabolism, enzymatic inhibition and toxicity of the pesticide fipronil

• Grant number: 16/15680-5
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: November 01, 2016
• End date: March 31, 2021
• Field of knowledge: Health Sciences - Pharmacy - Toxicological Analysis
• Principal Investigator: Anderson Rodrigo Moraes de Oliveira
• Grantee: Daniel Blascke Carrão
• Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 18/14668-7 - Development of a microfluidic analytical device for on-site quantification of pesticides after spraying in plants with citrus greening disease, BE.EP.DR

Abstract

Fipronil is a chiral pesticide worldwide employed in the control of insects. In Brazil, it has been used in several crops such as rice, potato, sugar cane, barley, bean, corn, soybean, among others. Despite enantiomers of chiral pesticides have the same physical-chemical properties; they may have enantioselective differences of activity, bioaccumulation, toxicity and metabolism. Although there are no significant differences in the biological activities of fipronil enantiomers in insects, enantioselective studies of toxicity and bioaccumulation of fipronil in green algae, fish and earthworms showed significant differences in the activities of the enantiomers. Enantioselective evaluations of metabolism and toxicity of this pesticide in non-target organisms, mainly humans, are extremely important for the risk assessment of this compound. The in vitro metabolism of racemic mixture of fipronil has already been evaluated. However, in vitro metabolism of each fipronil enantiomer was not individually determined. Therefore, this project aims to evaluate the metabolism of R-fipronil and S-fipronil, individually, to characterize the enzymatic kinetics and further to perform enzymatic inhibition studies as well as the evaluation of in vitro toxicity (cito- and genotoxicity) employing HepG2 culturing cells as human model.

Scientific publications

(10)

(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)

PEREZ DE ALBUQUERQUE, NAYARA CRISTINA; CARRAO, DANIEL BLASCKE; HABENSCHUS, MAISA DANIELA; MORAES DE OLIVEIRA, ANDERSON RODRIGO. Metabolism studies of chiral pesticides: A critical review. Journal of Pharmaceutical and Biomedical Analysis, v. 147, n. SI, p. 89-109, JAN 5 2018. (16/15680-5, 14/50945-4, 15/02533-1, 16/07597-0)

CARRAO, DANIEL BLASCKE; DOS REIS GOMES, ISABEL CRISTINA; BARBOSA JUNIOR, FERNANDO; MORAES DE OLIVEIRA, ANDERSON RODRIGO. Evaluation of the enantioselective in vitro metabolism of the chiral pesticide fipronil employing a human model: Risk assessment through in vitro-in vivo correlation and prediction of toxicokinetic parameters. Food and Chemical Toxicology, v. 123, p. 225-232, JAN 2019. (16/15680-5, 16/07597-0, 18/07534-4, 14/50945-4)

CARRAO, DANIEL BLASCKE; PEROVANI, ICARO SALGADO; PEREZ DE ALBUQUERQUE, NAYARA CRISTINA; MORAES DE OLIVEIRA, ANDERSON RODRIGO. Enantioseparation of pesticides: A critical review. TRAC-TRENDS IN ANALYTICAL CHEMISTRY, v. 122, JAN 2020. (14/50945-4, 16/15680-5, 18/14668-7, 18/07534-4)

DA SILVA, RODRIGO MOREIRA; CARRAO, DANIEL BLASCKE; HABENSCHUS, MAISA DANIELA; JIMENEZ, PAULA CHRISTINE; LOPS, NORBERTO PEPORINE; FENICAL, WILLIAM; COSTA-LOTUFO, LETICIA VERA; MORAES DE OLIVEIRA, ANDERSON RODRIGO. Prediction of seriniquinone-drug interactions by in vitro inhibition of human cytochrome P450 enzymes. TOXICOLOGY IN VITRO, v. 65, JUN 2020. (14/50265-3, 14/50945-4, 16/15680-5, 16/06366-5, 18/07534-4)

COSTA, EDNA M. A.; CARRAO, DANIEL B.; BUCCI, JADE L. M.; OLIVEIRA, ANDERSON R. M.; MACHADO, TALLITA M.; FERREIRA, VITOR F.; LIMA, EMERSON S.; VASCONCELLOS, MARNE C.; MAGALHAES, IGOR R. S.. CYP450 Metabolism of a Semisynthetic Naphthoquinone, an Anticancer Drug Candidate, by Human Liver Microsomes. Journal of the Brazilian Chemical Society, v. N/A, p. 9-pg., 2022-02-21. (18/07534-4, 16/15680-5)

PEREZ DE ALBUQUERQUE, NAYARA CRISTINA; CARRAO, DANIEL BLASCKE; HABENSCHUS, MAISA DANIELA; MORAES DE OLIVEIRA, ANDERSON RODRIGO. Metabolism studies of chiral pesticides: A critical review. Journal of Pharmaceutical and Biomedical Analysis, v. 147, p. 21-pg., 2018-01-05. (16/07597-0, 16/15680-5, 15/02533-1, 14/50945-4)

EDNA M. A. COSTA; DANIEL B. CARRÃO; JADE L. M. BUCCI; ANDERSON R. M. OLIVEIRA; TALLITA M. MACHADO; VITOR F. FERREIRA; ÉMERSON S. LIMA; MARNE C. VASCONCELLOS; IGOR R. S. MAGALHÃES. CYP450 Metabolism of a Semisynthetic Naphthoquinone, an Anticancer Drug Candidate, by Human Liver Microsomes. Journal of the Brazilian Chemical Society, v. 33, n. 10, p. 1145-1153, 2022-09-26. (18/07534-4, 16/15680-5)

PEREZ DE ALBUQUERQUE, NAYARA CRISTINA; CARRAO, DANIEL BLASCKE; HABENSCHUS, MAISA DANIELA; FONSECA, FRANCIELE SARAIVA; DA SILVA, RODRIGO MOREIRA; LOPES, NORBERTO PEPORINE; ROCHA, BRUNO ALVES; BARBOSA, JR., FERNANDO; MORAES DE OLIVEIRA, ANDERSON RODRIGO. Risk assessment of the chiral pesticide fenamiphos in a human model: Cytochrome P450 phenotyping and inhibition studies. Food and Chemical Toxicology, v. 146, DEC 2020. (14/50945-4, 16/15680-5, 15/02533-1)

CARRAO, DANIEL BLASCKE; HABENCHUS, MAISA DANIELA; PEREZ DE ALBUQUERQUE, NAYARA CRISTINA; DA SILVA, RODRIGO MOREIRA; LOPES, NORBERTO PEPORINE; MORAES DE OLIVEIRA, ANDERSON RODRIGO. In vitro inhibition of human CYP2D6 by the chiral pesticide fipronil and its metabolite fipronil sulfone: Prediction of pesticide-drug interactions. Toxicology Letters, v. 313, p. 196-204, OCT 1 2019. (16/07597-0, 14/50945-4, 16/15680-5, 18/14668-7, 18/07534-4)

CARRAO, DANIEL B.; DE OLIVEIRA, ANDERSON R. M.; MAGALHAES, IGOR R. S.. Challenges of probe cocktail approach for human drug-drug interaction assays. BIOANALYSIS, v. 10, n. 24, p. 4-pg., 2018-12-01. (16/15680-5)