Modulation of the multixenobiotic resistance mechanism in Danio rerio hepatocyte culture (ZF-L) after exposure to glyphosate and Roundup®

Chemosphere. 2019 Aug:228:159-165. doi: 10.1016/j.chemosphere.2019.04.140. Epub 2019 Apr 19.

Abstract

The presence of the transmembrane proteins of the ATP-binding cassette (ABC) family, which perform the efflux of several substances, contributes to the survival of aquatic organisms in a contaminated environmental. Those proteins provide a phenotype named the multixenobiotic resistance mechanism (MXR) by performing the efflux of a wide range of endogenous and exogenous compounds (ABCB) and biotransformation products and anionic compounds (ABCC). The aim of the present study was to evaluate the cellular defense pathway of an established culture from zebrafish hepatocytes (ZF-L) after 24 and 48 h of exposure to glyphosate and Original Roundup®, an herbicide used globally. Through abcb4, abcc1, abcc2 and abcc4 gene expression, ABCB and ABCC2 protein expression and ABC pump activity in ZF-L cells exposed to glyphosate and Roundup®. The results showed an increase in ABCB gene and protein expression; however, although ABCC2 showed an increase in gene expression, its protein expression was lower than in the control group. Regarding ABC activity, only exposure to Roundup® at the lowest concentration showed an increase at 48 h, but in the presence of inhibitors, both glyphosate and Roundup® appeared to modulate ABC activity, reducing its inhibition and returning activity to levels without inhibitor.

Keywords: ABC protein activity; Cell defense; Gene and protein expression; Herbicide; Zebrafish.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / drug effects
  • ATP-Binding Cassette Transporters / drug effects*
  • ATP-Binding Cassette Transporters / metabolism
  • Animals
  • Cells, Cultured
  • Drug Resistance, Multiple / drug effects*
  • Glycine / analogs & derivatives*
  • Glycine / pharmacology
  • Glyphosate
  • Hepatocytes / metabolism
  • Herbicides / pharmacology
  • Multidrug Resistance-Associated Protein 2
  • Multidrug Resistance-Associated Proteins / drug effects
  • Zebrafish / metabolism
  • Zebrafish Proteins / drug effects
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism

Substances

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP-Binding Cassette Transporters
  • Herbicides
  • Multidrug Resistance-Associated Protein 2
  • Multidrug Resistance-Associated Proteins
  • Zebrafish Proteins
  • Glycine