Evaluation of Endocrine Disrupting Potential of Pharmaceuticals That Are Exposed In Utero
Project no. 21680 · Status: Kapanmış · 2020
Summary
<p>With the increase in the use of industrial chemicals, humans can be exposed to many</p><p>chemicals in their daily lives, even at low doses. Some of these chemicals that cause adverse</p><p>effects by interacting with endocrine functions, are called “endocrine disruptors” (EDs). In</p><p>addition to industrial chemicals, pharmaceuticals can cause endocrine disrupting and</p><p>obesogenic effects as unintended adverse effects. There are limited studies that evaluate the</p><p>endocrine disrupting adverse effects of pharmaceuticals used during pregnancy.</p><p>Based on this information the present study aimed to investigate in vitro possible endocrine</p><p>disrupting potential of several pharmaceuticals that are prescribed safely during pregnancy,</p><p>namely paracetamol, indomethacin, alpha-methyldopa and pantoprazole. In order to</p><p>determine the endocrine disrupting effects aromatase inhibitor, estrogen receptor (ER)</p><p>agonistic/antagonistic and steroidogenesis inhibitor/inducer effects of the pharmaceuticals</p><p>were investigated.</p><p>Paracetamol and indomethacin observed to inhibit aromatase activity in a dose-dependent</p><p>manner at their higher tested concentrations.</p><p>In terms of ER agonistic effect, indomethacin showed a biphasic effect, while alphamethyldopa</p><p>increased cell proliferation only at its low concentrations. Among the tested</p><p>pharmaceuticals, only pantoprazole had ER antagonistic effect. Considering the effects of</p><p>pharmaceuticals on steroidogenesis pathway, paracetamol, indomethacin, and pantoprazole</p><p>increased estradiol levels, while paracetamol significantly decreased testosterone levels at all</p><p>tested concentrations in H295R cells.</p><p>On the contrary, alpha-methyldopa increased estradiol levels at all tested concentrations and it</p><p>was thought to exert this effect through aromatase induction in the steroidogenesis pathway.</p><p>In conclusion, all four drugs may have potential EB and/or adipogenic effects through</p><p>different mechanisms, which were tried to be elucidated with different in vitro studies.</p><p>The potential of these pharmaceuticals to cause reproductive dysfunction later in life,</p><p>especially as a result of in utero exposure, should be investigated by further in vivo and</p><p>epidemiological studies.</p>