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Efficient in vivo and in silico assessments of antiandrogenic potential in zebrafish.
- Source :
-
Comparative Biochemistry & Physiology Part C: Toxicology & Pharmacology . Feb2023, Vol. 264, pN.PAG-N.PAG. 1p. - Publication Year :
- 2023
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Abstract
- This study aimed to establish zebrafish-based in vivo and in silico assay systems to evaluate the antiandrogenic potential of environmental chemicals. Zebrafish embryos were exposed to 17α-methyltestosterone (TES) alone or coexposed to TES and representative antiandrogens including flutamide, p,p ′-DDE, vinclozolin, fenitrothion, and linuron. We assessed the transcript expression of the androgen-responsive gene sulfotransferase family 2, cytosolic sulfotransferase 3 (sult2st3). The expression of sult2st3 was significantly induced by TES in the later stages of embryonic development. However, the TES-induced expression of sult2st3 was inhibited by flutamide in a concentration-dependent manner (IC 50 : 5.7 μM), suggesting that the androgen receptor (AR) plays a role in sult2st3 induction. Similarly, p,p ′-DDE, vinclozolin, and linuron repressed the TES-induced expression of sult2st3 (IC 50s : 0.35, 3.9, and 52 μM, respectively). At the highest concentration tested (100 μM), fenitrothion also suppressed sult2st3 expression almost completely. Notably, p,p ′-DDE and linuron did not inhibit sult2st3 induction due to higher concentrations of TES; instead, they potentiated TES-induced sult2st3 expression. Fenitrothion and linuron, which had relatively low antiandrogenic potentials in terms of sult2st3 inhibition, induced broader toxicities in zebrafish embryos; thus, the relationship between developmental toxicities and antiandrogenic potency was unclear. Additionally, an in silico docking simulation showed that all five chemicals interact with the zebrafish AR at relatively low interaction energies and with Arg702 as a key amino acid in ligand binding. Our findings suggest that a combination of zebrafish-based in vivo and in silico assessments represents a promising tool to assess the antiandrogenic potentials of environmental chemicals. [Display omitted] • Zebrafish sult2st3 is a good biomarker to assess antiandrogenic potency of chemicals. • Androgen receptor (AR) plays a key role in sult2st3 induction by androgen. • Factors that influence in vivo antiandrogenic potency are discussed. • Arg702 is a key amino acid residue for the antiandrogen binding with AR. • A combination of in vivo and in silico methods is useful for testing antiandrogenicity. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15320456
- Volume :
- 264
- Database :
- Academic Search Index
- Journal :
- Comparative Biochemistry & Physiology Part C: Toxicology & Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 160963658
- Full Text :
- https://doi.org/10.1016/j.cbpc.2022.109513