Science Inventory

P-glycoprotein Inhibition by the Agricultural Pesticide Propiconazole and Its Hydroxylated Metabolites: Implications for Pesticide-Drug Interactions.

Citation:

Mazur, Chris, S. Marchitti, AND J. Zastre. P-glycoprotein Inhibition by the Agricultural Pesticide Propiconazole and Its Hydroxylated Metabolites: Implications for Pesticide-Drug Interactions. Presented at 19th North American ISSX Meeting, San Francisco, CA, October 19 - 23, 2014.

Impact/Purpose:

Poster presented at 19th North American ISSX Meeting.

Description:

The human efflux transporter P-glycoprotein (P-gp; MDR1) functions an important cellular defense system against a variety of xenobiotics; however, little information exists on whether environmental chemicals interact with P-gp. Conazoles provide a unique challenge to exposure assessment because of their use as both pesticides and drugs. Propiconazole is an agricultural pesticide undergoing evaluation by the U.S. Environmental Protection Agency’s Endocrine Disruptor Screening Program. In this study, the P-gp interaction of propiconazole and its hydroxylated metabolites were evaluated using MDR1-expressing membrane vesicles and NIH-3T3/MDR1 cells. Membrane vesicle assays demonstrated propiconazole (IC50,122.9 µM) and its metabolites (IC50s, 350.8 µM, 366.4 µM, and 456.3 µM) inhibited P-gp efflux of a probe substrate, with propiconazole demonstrating the strongest interaction. P-gp mediated transport of propiconazole in MDR1-expressed vesicles was not detected indicating propiconazole interacts with P-gp as an inhibitor rather than a substrate. In NIH-3T3/MDR1 cells, propiconazole (1 and 10 µM) led to decreased cellular resistance (chemosensitization) to paclitaxel, a chemotherapeutic drug and known MDR1substrate. Collectively, these results have pharmacokinetic and risk assessment implications as P-gp interaction may influence pesticide toxicity and the potential for pesticide-drug interactions.

URLs/Downloads:

http://www.issx.org/?page=JSSX_ISSX   Exit

Record Details:

Record Type: DOCUMENT (PRESENTATION/POSTER)
Product Published Date: 10/23/2014
Record Last Revised: 08/12/2015
OMB Category: Other
Record ID: 294637