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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

In vitro inhibition of human CYP2D6 by the chiral pesticide fipronil and its metabolite fipronil sulfone: Prediction of pesticide-drug interactions

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Carrao, Daniel Blascke [1] ; Habenchus, Maisa Daniela [1] ; Perez de Albuquerque, Nayara Cristina [1] ; da Silva, Rodrigo Moreira [2] ; Lopes, Norberto Peporine [2] ; Moraes de Oliveira, Anderson Rodrigo [1, 3]
Total Authors: 6
[1] Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, Dept Quim, Av Bandeirantes 3900, BR-14040901 Ribeirao Preto, SP - Brazil
[2] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Fis & Quim, BR-14090903 Ribeirao Preto, SP - Brazil
[3] UNESP, Inst Chem, Natl Inst Alternat Technol Detect Toxicol Evaluat, POB 355, BR-14800900 Araraquara, SP - Brazil
Total Affiliations: 3
Document type: Journal article
Source: Toxicology Letters; v. 313, p. 196-204, OCT 1 2019.
Web of Science Citations: 0

Fipronil is a chiral insecticide employed worldwide in crops, control of public hygiene and control of veterinary pests. Humans can be exposed to fipronil through occupational, food, and environmental contamination. Therefore, the risk assessment of fipronil in humans is important to protect human health. Fipronil sulfone is the major metabolite formed during fipronil metabolism by humans. Since the CYP450 enzymes are the main ones involved in drug metabolism, the evaluation of their inhibition by fipronil and its main metabolite is important to predict drug-pesticide interactions. The aim of this work was to investigate the inhibition effects of rac-fipronil, S-fipronil, R-fipronil and fipronil sulfone on the main human CYP450 isoforms. The results showed that CYP2D6 is the only CYP450 isoform inhibited by these xenobiotics. In addition, no enantioselective differences were observed in the inhibition of CYP450 isoforms by fipronil and its individuals' enantiomers. Rac-fipronil, S-fipronil and R-fipronil are moderate CYP2D6 inhibitors showing a competitive inhibition profile. On the other hand, the metabolite fipronil sulfone showed to be a strong inhibitor of CYP2D6 also by competitive inhibition. These results highlight the importance of metabolite evaluation on pesticide safety since the metabolism of fipronil into fipronil sulfone increases the risk of pesticide-drug interactions for drugs metabolized by CYP2D6. (AU)

FAPESP's process: 16/07597-0 - Development of chromatographic/electrophoretic methods to be further used in in vitro enzymatic inhibition and drug interaction of chiral pesticides
Grantee:Anderson Rodrigo Moraes de Oliveira
Support type: Regular Research Grants
FAPESP's process: 14/50945-4 - INCT 2014: National Institute for Alternative Technologies of Detection, Toxicological Evaluation and Removal of Micropollutants and Radioactivies
Grantee:Maria Valnice Boldrin
Support type: Research Projects - Thematic Grants
FAPESP's process: 16/15680-5 - Enantioselective in vitro studies of metabolism, enzymatic inhibition and toxicity of the pesticide fipronil
Grantee:Daniel Blascke Carrão
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 18/14668-7 - Development of a microfluidic analytical device for on-site quantification of pesticides after spraying in plants with citrus greening disease
Grantee:Daniel Blascke Carrão
Support type: Scholarships abroad - Research Internship - Doctorate
FAPESP's process: 18/07534-4 - Development of chromatographic / electrophoretic methods to be further applied in in vitro enzymatic inhibition studies and prediction of drug interactions of chiral pesticides - Phase 2
Grantee:Anderson Rodrigo Moraes de Oliveira
Support type: Regular Research Grants