Title:Evaluation of Endocrine Related Adverse Effects of Non-Endocrine Targeted
Pharmaceuticals in Cellular Systems
Volume: 23
Issue: 14
Author(s): Bita Entezari, Deniz Bozdag and Hande Gurer-Orhan*
Affiliation:
- Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Ege University, 35040, Izmir, Turkey
Keywords:
Paracetamol, indomethacin, alpha-methyldopa, pantoprazole, endocrine related adverse effect, EDCs.
Abstract: Background: Prenatal period is a critical developmental phase that is sensitive to hormonal
disruption by natural and/or exogenous hormones. Some pharmaceuticals frequently prescribed and used
safely during pregnancy are shown to interact with the developmental programming of fetus, resulting in
endocrine-related adverse effects.
Objective: In this research, we aimed to determine the endocrine disrupting potential of paracetamol,
indomethacin, alpha-methyldopa and pantoprazole which are frequently prescribed pharmaceuticals during pregnancy.
Methods: In vitro aromatase inhibitory, estrogen receptor (ER) agonist/antagonist (E-Screen assay) and
hormone biosynthesis modulatory effects (H295R steroidogenesis assay) of the selected pharmaceuticals
were evaluated. Furthermore, their effects on viability of MCF-7/BUS and H295R cells were also evaluated by MTT assay.
Results: None of the pharmaceuticals affected H295R cell viability. Only indomethacin reduced MCF-
7/BUS cell viability at 100μM and 300μM. Among the tested pharmaceuticals, only paracetamol and
indomethacin showed aromatase inhibitory activity with IC50 values of 14.7 x 10-5 M and 57.6 x 10-5 M,
respectively. Moreover, indomethacin displayed a biphasic ER agonist effect. ER antagonist effects of
indomethacin and pantoprazole were confirmed by performing two stepped E-Screen assay. After the
partial validation of the H295R steroidogenesis assay with forskolin and prochloraz, the effects of pharmaceuticals
on synthesis of testosterone (T) and estradiol (E2) levels were tested. Alpha-methyldopa
increased E2 at all tested concentrations and T at 1.48 and 4.4μM. Contrarily other tested pharmaceuticals
did not affect steroidogenesis.
Conclusion: Present data suggest that all tested pharmaceuticals may have potential endocrine disrupting
effect, which should be considered when used in pregnancy.
