Effect of Glyphosate and AMPA on expression and activity of ABC export proteins in killifish (Fundulus heteroclitus) kidney tubules

Glyphosate (Gly), the world’s most-used herbicide, and its degradation product aminomethylphosphonic acid (AMPA) are frequently detected in ecosystems. Both are linked to adverse effects in fish, yet their impact on detoxification systems is not fully characterized. We investigated their effects on ATP-binding-cassette transporters in renal proximal tubules of Atlantic killifish, a model for xenobiotic transport. Tubules were exposed to Gly or AMPA at 1, 10, 100 µg/L for 30 minutes, and 10 µg/L for 24 hours. Transporter function was assessed by fluorescent substrate accumulation and protein expression by immunostaining. Short-term exposure reduced Pgp, Mrp2, Mrp4, and Bcrp activity, long-term exposure upregulated transport and expression, partly via AhR and PxR pathways. In vitro -results were confirmed in vivo after exposure of killifish to 10 µg/L Gly for 24 h. This study provides insight into pesticide-induced modulation of detoxification in aquatic vertebrates and highlights ABC transporters as early biomarkers of pollutant exposure. • ABC transporters’ function can be assessed by accumulation of fluorescent substrates in renal tubular lumens of killifish • Short-term exposure to Gly and AMPA leads to decreased transporter function • Long-term exposure results in induced expression of Pgp, Mrp2, Mrp4 and Bcrp • Transporter upregulation is mediated by nuclear receptors