Differential interactions of carbamate pesticides with drug transporters

Abstract

1. Pesticides are now recognised to interact with drug transporters, but only few data are available on this issue for carbamate pesticides, a widely-used class of agrochemicals, to which humans are highly exposed. The present study was therefore designed to determine whether four representative carbamate pesticides, i.e., the insecticides aminocarb and carbofuran, the herbicide chlorpropham and the fungicide propamocarb, may impair activities of main drug transporters implicated in pharmacokinetics. 2. The interactions of carbamates with solute carrier and ATP-binding cassette transporters were investigated using cultured transporter-overexpressing cells, reference substrates and spectrofluorimetry-, liquid chomatography/tandem mass spectrometry-or radioactivity-based methods. 3. Aminocarb and carbofuran exerted no or minimal effects on transporter activities, whereas chlorpropham inhibited BCRP and OAT3 activities and propamocarb decreased those of OCT1 and OCT2, but cis-stimulated that of MATE2-K. Such alterations of transporters however required chlorpropham/propamocarb concentrations in the 5-50 µM range, likely not relevant to environmental exposure. Trans-stimulation assays and propamocarb accumulation experiments additionally suggested that propamocarb is not a substrate for OCT1, OCT2 and MATE2-K. 4. These data indicate that some carbamate pesticides can interact in vitro with some drug transporters, but only when used at concentrations higher than those expected to occur in environmentally-exposed humans.

Functional and Pharmacological Comparison of Human, Mouse, and Rat Organic Cation Transporter 1 toward Drug and Pesticide Interaction

“…The hOCT1-, mOct1-, and rOct1-mediated MPP uptake was decreased between 3% and 75%. The inhibition of OCT1 and OCT2 as well the stimulation of MATE2K by propamocarb was reported by Guéniche et al (2020), but the study also confirmed that propamocarb is not a substrate of the cation transporter [ 44 ]. To our knowledge, up to now, there is no data that showed the excretion of propamocarb in urine.…”

Transporter-interfering chemicals inhibit P-glycoprotein of yellowfin tuna (Thunnus albacares)

“…This study builds upon previous structural, functional, and environmental studies (Bruyere et al, 2017;Chedik et al, 2019Chedik et al, , 2018Epel et al, 2008;Fardel et al, 2012;Guéniche et al, 2020aGuéniche et al, , 2020bLuckenbach and Epel, 2005;Nicklisch et al, 2017aNicklisch et al, , 2016Smital et al, 2004;Stevenson et al, 2006) to probe potential similarities and differences in how XTs from humans and the species they consume may interact with common pollutants. It further sheds light on how chemicals that may interfere with these transporters in humans, i.e., TICs, might also act in the species that carry them.…”

Interactions of Environmental Chemicals and Natural Products With ABC and SLC Transporters in the Digestive System of Aquatic Organisms

“…Members of both the ABC and SLC-type families have been shown to be part of a highly conserved defense mechanism against chemical insults, often referred to as multidrug-resistance (MDR) transporters ( Ling, 1997 ; Gottesman et al, 2002 ; Glavinas et al, 2004 ; Leslie et al, 2005 ; Sharom, 2008 ; Giacomini et al, 2010 ; Hillgren et al, 2013 ; Nigam, 2015 ). The mammalian homologs of these transporter superfamilies have been extensively studied in the past, unraveling their precise molecular interactions with drugs and environmental chemicals ( Juliano and Ling, 1976 ; Beck, 1987 ; Horio et al, 1988 ; Hediger et al, 2004 ; Oosterhuis et al, 2008 ; Staud et al, 2013 ; Nicklisch et al, 2016 ; Chedik et al, 2019 ; Guéniche et al, 2020 ; Nicklisch and Hamdoun, 2020 ).…”