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 min, and 10 µg/L for 24 h. 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.