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Effects of central nervous system drugs on androgen, estrogen α, glucocorticoid, and thyroid receptors
ID Kenda, Maša (Avtor), ID Zore, Taja (Avtor), ID Sollner Dolenc, Marija (Avtor)

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Izvleček
Some drugs that act on the central nervous system (CNS) are known to affect the endocrine system, although the mechanisms of endocrine toxicity are not well characterized to date. Such CNS drugs include antipsychotics, anticonvulsants, and antidepressants. In the present study, in-vitro firefly luciferase reporter-gene assays using the AR-EcoScreen assay using Chinese hamster ovary (CHO) cell line, hERα-HeLa9903, MDA-kb2, and GH3.TRE-Luc cell lines were used to determine the effects of nine CNS drugs on the androgen receptor, estrogen receptor α, glucocorticoid receptor, and thyroid hormone receptor, respectively. In the AR-EcoScreen assay using CHO cells, anti-androgenic activities were shown for carbamazepine (IC$_{50}$, 167 μM), clonazepam (IC$_{50}$, 26.7 μM), eslicarbazepine acetate (IC$_{50}$, 375 μM), fluoxetine (at 25 μM), lorazepam (IC$_{50}$, 16.4 μM), and sertraline (IC$_{50}$, 8.7 μM). In the hERα-HeLa-9903 cells, estrogen receptor α agonistic activities were shown for fluoxetine, paroxetine, and sertraline (at 10 μM and 25 μM), and in the GH3.TRE-Luc cells, the same three CNS drugs showed antithyroid activities (IC$_{50}$s, 11.6, 11.9, 2.7 μM, respectively). In the hERα-HeLa-9903 cells, estrogen receptor α antagonistic activities were shown for carbamazepine (IC$_{50}$, 114.3 μM), clonazepam (IC$_{50}$, 52.9 μM), and eslicarbazepine acetate (IC$_{50}$, 376.6 μM). When the CNS drugs were tested in the MDA-kb2 cells, none of them showed any activities toward glucocorticoid receptors. Little to no effects were seen toward any of these nuclear receptors for paliperidone and risperidone. The increased signal in the estrogen receptor α agonism assay seen for fluoxetine and paroxetine was confirmed to be mediated through estrogen receptor α. Additionally, we examined the interference of these CNS drugs with the firefly luciferase enzyme. These data elucidate the potential for adverse endocrine effects for some of these CNS drugs, which should therefore contribute to informed choice when prescribing them. However, long-term exposure to therapeutic concentrations of CNS drugs that have activities on the endocrine system should be explored further also in vivo.

Jezik:Angleški jezik
Ključne besede:central nervous system drugs, hormonal effects, endocrine toxicity, nuclear receptors, reporter-gene assays
Vrsta gradiva:Članek v reviji
Tipologija:1.01 - Izvirni znanstveni članek
Organizacija:FFA - Fakulteta za farmacijo
Status publikacije:Objavljeno
Različica publikacije:Objavljena publikacija
Leto izida:2022
Št. strani:8 str.
Številčenje:Vol. 363, art. 110030
PID:20.500.12556/RUL-139687 Povezava se odpre v novem oknu
UDK:612.43:620.266.1
ISSN pri članku:0009-2797
DOI:10.1016/j.cbi.2022.110030 Povezava se odpre v novem oknu
COBISS.SI-ID:112819203 Povezava se odpre v novem oknu
Datum objave v RUL:06.09.2022
Število ogledov:869
Število prenosov:88
Metapodatki:XML RDF-CHPDL DC-XML DC-RDF
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Gradivo je del revije

Naslov:Chemico-biological interactions
Skrajšan naslov:Chem.-biol. interact.
Založnik:Elsevier
ISSN:0009-2797
COBISS.SI-ID:1720335 Povezava se odpre v novem oknu

Licence

Licenca:CC BY-NC-ND 4.0, Creative Commons Priznanje avtorstva-Nekomercialno-Brez predelav 4.0 Mednarodna
Povezava:http://creativecommons.org/licenses/by-nc-nd/4.0/deed.sl
Opis:Najbolj omejujoča licenca Creative Commons. Uporabniki lahko prenesejo in delijo delo v nekomercialne namene in ga ne smejo uporabiti za nobene druge namene.

Sekundarni jezik

Jezik:Slovenski jezik
Ključne besede:zdravila za osrednji živčni sistem, hormonski učinki, endokrina toksičnost, jedrski receptorji, testi reporterskega gena, hormonski motilci, endokrinologija

Projekti

Financer:ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
Program financ.:Young researchers

Financer:ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
Številka projekta:P1-0208
Naslov:Farmacevtska kemija: načrtovanje, sinteza in vrednotenje učinkovin

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