Evaluation of the effect of the herbicide glyphosate and its main metabolite, aminomethylphosphonic acid (AMPA), on human cytochrome P450 (CYP450) enzymes

• Grant number: 25/04629-8
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2025
• End date: January 31, 2027
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Analytical Chemistry
• Principal Investigator: Anderson Rodrigo Moraes de Oliveira
• Grantee: Arthur Avila
• Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Glyphosate is the most widely used pesticide in Brazil and worldwide and is used in many crops, such as rice, coffee, sugarcane, beans, corn, soybeans and wheat. Due to its massive use in agriculture and frequent use in the composition of household cleaning products, several studies have warned about the contamination of water bodies, atmospheric air and food. As a result, there is great concern about human exposure, since this pesticide and its metabolite, aminomethylphosphonic acid (AMPA), have already been found in biological fluids of individuals living in both agricultural and urban areas. In the human body, xenobiotics can be metabolized by cytochrome P450 (CYP450) enzymes or inhibit their enzymatic activity, resulting in pesticide-drug interactions. Therefore, the evaluation of the effect of glyphosate in human models is an important and necessary work in identifying possible damages to human health. The objective of this research project is to evaluate, in vitro, the effect of glyphosate and its metabolite, AMPA, on the main CYP450 isoforms involved in drug metabolism and to perform in vitro-in vivo extrapolation of the results. To this end, the toxicokinetic parameters hepatic clearance, hepatic extraction rate and bioavailable fraction of the pesticide will be determined. In addition, phenotyping studies and evaluation of the inhibitory potential of glyphosate will be performed to investigate and predict pesticide-drug interactions. (AU)