Evaluation of Endocrine Related Adverse Effects of Non-Endocrine Tar-geted Pharmaceuticals in Cellular Systems
Küçük Resim Yok
Tarih
2023
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Bentham Science Publishers
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
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 100?M and 300?M. 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 4.4?M. 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. © 2023 Bentham Science Publishers.
Açıklama
Anahtar Kelimeler
alpha-methyldopa, EDCs, endocrine related adverse effect, indomethacin, pantoprazole, Paracetamol, 7 hydroxy 4 trifluoromethyl coumarin, 7 methoxy 4 trifluoromethyl coumarin, antiestrogen, cytochrome P450 family 19, endocrine disruptor, estradiol, estrogen, estrogen receptor, estrogen receptor antagonist, indometacin, ketoconazole, methyldopa, pantoprazole, paracetamol, prochloraz, progesterone, testosterone, unclassified drug, Article, biosynthesis, cell proliferation, cell viability, clinical evaluation, controlled study, cytotoxicity, cytotoxicity assay, drug solubility, drug synthesis, EC50, endocrine system, enzyme linked immunosorbent assay, estrogen activity, gene expression, gestational age, hormone determination, hormone synthesis, human, human cell, IC50, medicinal chemistry, MTT assay, NCI-H295R cell line, optical density, protein function, screening test, steroidogenesis
Kaynak
Endocrine, Metabolic and Immune Disorders - Drug Targets
WoS Q Değeri
Scopus Q Değeri
Q3
Cilt
23
Sayı
14
