A microfluidic device for inhibition studies with human cytochrome P450 enzymes

• Grant number: 22/00127-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: September 01, 2022
• End date: August 31, 2023
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Analytical Chemistry
• Principal Investigator: Anderson Rodrigo Moraes de Oliveira
• Grantee: Icaro Salgado Perovani
• Supervisor: Charles Henry
• Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Colorado State University, United States
• Associated to the scholarship: 20/02139-0 - 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, BP.DR

Abstract

Pesticide exposure represents a significant health concern with significant impacts reported for both acute and chronic exposure. Pesticide-drug interactions are believed to play a role in the toxicity of pesticides due to the inhibition of CYP450 forms responsible for drug metabolism by pesticides. These interactions can lead to adverse effects or even lack of drug activity due to the interactions. Studying these interactions is important as the use of pesticides in food production increases along with increased human exposure. For instance, the CYP3A4 form is an important CYP form responsible for the metabolism of many common drugs. For this reason, from a risk assessment standpoint, characterizing the inhibition potential of a pesticide with CYP3A4 can help understand the risks associated with exposure to that pesticide. Developing studies like this is a laborious task as it generally involves many samples and expensive laboratory equipment. Increasing the efficiency of the inhibition studies by performing inhibition screening assays has already been done with colorimetric inhibition screening kits. These kits decrease the cost and time required to develop these studies since only the CYP forms significantly inhibited will move on to the next steps. Miniaturization of these assays can help further decrease the laboratory cost associated with these inhibition screening assays and be helpful towards increasing the efficiency of developing inhibition studies. Microfluidic devices offer a method to further miniaturize these assays. Hence, microfluidic devices in conjunction with the colorimetric inhibition assays can be an important tool to decrease the cost of the CYP450 inhibition studies and accelerate the rate of the information obtained about the chemical under study. (AU)