Evaluation of Endocrine Related Adverse Effects of Non-Endocrine Targeted Pharmaceuticals in Cellular Systems
Makaleler > Tam Makale · 2023
Yazarlar: Bita Entezari, Deniz Bozdağ, Hande GÜRER ORHAN
Endocrine, Metabolic & Immune Disorders - Drug Targets, SCI Expanded İndekslerine Giren Dergi, Uluslararası, Wos, 2023, cilt 23, ss 1740-1749
DOI: 10.2174/1871530323666230224145624
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: 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.