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AHR2 knockdown prevents PAH-mediated cardiac toxicity and XRE- and ARE-associated gene induction in zebrafish (Danio rerio).

Publication ,  Journal Article
Van Tiem, LA; Di Giulio, RT
Published in: Toxicology and applied pharmacology
August 2011

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants often present in aquatic systems as complex mixtures. Embryonic fish are sensitive to the developmental toxicity of some PAHs, but the exact mechanisms involved in this toxicity are still unknown. This study explored the role of the aryl hydrocarbon receptor (AHR) in the oxidative stress response of zebrafish to the embryotoxicity of select PAHs. Embryos were exposed to two PAHs, benzo[k]fluoranthene (BkF; a strong AHR agonist) and fluoranthene (FL; a cytochrome P4501A (CYP1A) inhibitor), alone and in combination. CYP1A, CYP1B1, CYP1C1, and redox-responsive genes glutathione s-transferase pi 2 (GSTp2), glutathione peroxidase 1 (GPx1), the glutamate-cysteine ligase catalytic subunit (GCLc), MnSOD and CuZnSOD mRNA expression was examined. CYP1 activity was measured via an in vivo ethoxyresorufin-O-deethlyase (EROD) activity assay, and the area of the pericardium was measured as an index of cardiotoxicity. BkF or FL alone caused no deformities whereas BkF+FL resulted in extreme pericardial effusion. BkF induced CYP activity above controls and co-exposure with FL inhibited this activity. BkF induced expression of all three CYPs, GSTp2, and GCLc. BkF+FL caused greater than additive induction of the three CYPs, GSTp2, GPx1, and GCLc but had no effect on MnSOD or CuZnSOD. AHR2 knockdown protected against the cardiac deformities caused by BkF+FL and significantly inhibited the induction of the CYPs, GSTp2, GPx1, and GCLc after BkF+FL compared to non-injected controls. These results further show the protective role of AHR2 knockdown against cardiotoxic PAHs and the role of AHR2 as a mediator of redox-responsive gene induction.

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Published In

Toxicology and applied pharmacology

DOI

EISSN

1096-0333

ISSN

0041-008X

Publication Date

August 2011

Volume

254

Issue

3

Start / End Page

280 / 287

Related Subject Headings

  • Zebrafish Proteins
  • Zebrafish
  • Xenobiotics
  • Transcriptional Activation
  • Toxicology
  • Response Elements
  • Receptors, Aryl Hydrocarbon
  • Polycyclic Aromatic Hydrocarbons
  • Gene Knockdown Techniques
  • Embryo, Nonmammalian
 

Citation

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Van Tiem, L. A., & Di Giulio, R. T. (2011). AHR2 knockdown prevents PAH-mediated cardiac toxicity and XRE- and ARE-associated gene induction in zebrafish (Danio rerio). Toxicology and Applied Pharmacology, 254(3), 280–287. https://doi.org/10.1016/j.taap.2011.05.002
Van Tiem, Lindsey A., and Richard T. Di Giulio. “AHR2 knockdown prevents PAH-mediated cardiac toxicity and XRE- and ARE-associated gene induction in zebrafish (Danio rerio).Toxicology and Applied Pharmacology 254, no. 3 (August 2011): 280–87. https://doi.org/10.1016/j.taap.2011.05.002.
Van Tiem LA, Di Giulio RT. AHR2 knockdown prevents PAH-mediated cardiac toxicity and XRE- and ARE-associated gene induction in zebrafish (Danio rerio). Toxicology and applied pharmacology. 2011 Aug;254(3):280–7.
Van Tiem, Lindsey A., and Richard T. Di Giulio. “AHR2 knockdown prevents PAH-mediated cardiac toxicity and XRE- and ARE-associated gene induction in zebrafish (Danio rerio).Toxicology and Applied Pharmacology, vol. 254, no. 3, Aug. 2011, pp. 280–87. Epmc, doi:10.1016/j.taap.2011.05.002.
Van Tiem LA, Di Giulio RT. AHR2 knockdown prevents PAH-mediated cardiac toxicity and XRE- and ARE-associated gene induction in zebrafish (Danio rerio). Toxicology and applied pharmacology. 2011 Aug;254(3):280–287.
Journal cover image

Published In

Toxicology and applied pharmacology

DOI

EISSN

1096-0333

ISSN

0041-008X

Publication Date

August 2011

Volume

254

Issue

3

Start / End Page

280 / 287

Related Subject Headings

  • Zebrafish Proteins
  • Zebrafish
  • Xenobiotics
  • Transcriptional Activation
  • Toxicology
  • Response Elements
  • Receptors, Aryl Hydrocarbon
  • Polycyclic Aromatic Hydrocarbons
  • Gene Knockdown Techniques
  • Embryo, Nonmammalian