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Endocrine disrupting activities and immunomodulatory effects in lymphoblastoid cell lines of diclofenac, 4-hydroxydiclofenac and paracetamol [Elektronski vir]Klopčič, Ivana ...A critical literature review reveals that knowledge of side effects of pharmaceuticals diclofenac and paracetamol is extremely important because of their widespread use and occurrence in the ... environment. In order to delineate whether these compounds have endocrine activity and influence on the immune system, we assessed the potential endocrine disrupting and immunomodulatory activities of: diclofenac (DIC), its metabolite 4-hydroxydiclofenac (4-HD) and paracetamol (PAR). Herein, we report on their impact on estrogen receptor (ER), androgen receptor (AR), glucocorticoid receptor (GR) and thyroid hormone receptor (TR). The endocrine disrupting effects were assessed in vitro in MDA-kb2 and GH3.TRE-Luc cell lines and by the XenoScreen YES/YAS assay. Moreover, binding affinity to nuclear receptors (GR and AR) was also measured. Immunomodulatory properties of the compounds were evaluated in lymphoblastoid cell lines. All the tested compounds showed endocrine disrupting and immunomodulatory activities. The results revealed that both DIC and its metabolite 4-HD exhibited significant estrogenic, anti-androgenic (in YAS assay), (anti)-androgenic, (anti)-glucocorticoid and anti-thyroid hormonal activities (in luciferase reporter gene assays). DIC showed direct binding to the GR, while its metabolite 4-HD to the GR and AR. Only metabolite 4-HD showed estrogenic, androgenic (in YAS assay) and thyroid-hormonal activities. PAR had anti-androgenic activity and anti-thyroid hormonal activity. PAR displayed GR agonist activity with competition to its receptor and agonistic activity to AR. All of the compounds significantly modulated pro-inflammatory and immunoregulatory cytokine production in lymphoblastoid cell lines and were thus proven immunomodulatory. The study is useful in determining toxicological effects and contributes to the knowledge of possible side effects of diclofenac, its metabolite and paracetamol.Source: Toxicology letters. - ISSN 0378-4274 (Vol. 294, Sept. 2018, str. 95-104)Type of material - e-article ; adult, seriousPublish date - 2018Language - englishCOBISS.SI-ID - 4397681
Author
Klopčič, Ivana |
Markovič, Tijana |
Mlinarič-Raščan, Irena |
Sollner Dolenc, Marija
Topics
Imunomodulatorji |
Endokrinologija |
diclofenac |
4-hydroxydiclofenac |
paracetamol |
endocrine disruption |
immunomodulatory property |
estrogen receptor |
androgen receptor |
glucocorticoid receptor |
thyroid hormone receptor
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Database name | Field | Year |
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Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
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Klopčič, Ivana | 39548 |
Markovič, Tijana | 34223 |
Mlinarič-Raščan, Irena | 12443 |
Sollner Dolenc, Marija | 08519 |
Source: Personal bibliographies
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