The insecticide Chlorpyrifos modifies the expression of genes involved in the PXR and PXR-AhR pathways in the rainbow trout, Oncorhynchus mykiss.

DE ANNA, J.S.; ARIAS DARRAZ, L.; PAINEFILÚ, J.C.; CÁRCAMO J.G.; ALVES-MOURA, P; VENTURINO A.; LUQUET, C.M.

PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY

ACADEMIC PRESS INC ELSEVIER SCIENCE

Lugar: Amsterdam; Año: 2021 vol. 178 p. 1 - 10

0048-3575

Chlorpyrifos (CPF) is a broad-spectrum organophosphate pesticide, reported as the second most commonly detected in water and food. Despite CPF toxicity on non-target aquatic species has been extensively studied, there are still few studies that address the effects of CPF on key transcriptional pathways in fish. The Pregnane X receptor (PXR) is a nuclear receptor that can be activated by binding to a wide variety of ligands and regulates the transcription of enzymes involved in the metabolism and transport of many endogenous and exogenous compounds in vertebrates, including fish. We evaluated the effect of CPF on the mRNA expression of PXR-regulated-genes (PXR, CYP3A27, CYP2K1, ABCB1, UGT, and ABCC2) in the intestine and liver of the rainbow trout, O. mykiss, exposed in vivo to an environmentally relevant CPF concentration. Our results demonstrate that, albeit different kinetics, the expression of PXR and PXR-regulated genes is increased in the liver and intestine of O. mykiss upon exposure to CPF. Additionally, we evaluated the impact of CPF exposure on other cellular pathways involved in xenobiotic metabolism, such as the Aryl Hydrocarbon Receptor (AhR) pathway, and on the expression and activity of different biotransformation enzymes (CYP2M1, GST, FMO1,or cholinesterases (ChEs)). In contrast to PXR, the expression of the AhR, and its target gene CYP1A, are reduced upon CPF exposure. Furthermore, ChE and CYP1A activities are significantly inhibited by CPF, in both the intestine and the liver.We can conclude that CPF activates the PXR pathway in O. mykiss in the intestine and liver, with a more profound effect in the intestine. Likewise, our results support regulatory crosstalk between PXR and AhR pathways, where the induction of PXR coincides with the downregulation of AhR-mediated CYP1A mRNA expression and activity in the intestine.