Comparative effects of di-(2-ethylhexyl)phthalate ...
Document type :
Article dans une revue scientifique: Article original
DOI :
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Title :
Comparative effects of di-(2-ethylhexyl)phthalate and di-(2-ethylhexyl)terephthalate metabolites on thyroid receptors: in vitro and in silico studies
Author(s) :
KAMBIA, Nicolas [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - ULR 7365
Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 [GRITA]
Severin, Isabelle [Auteur]
Equipe NuTox (LNC - U1231) [NUTOX]
Farce, Amaury [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Lille Inflammation Research International Center - U 995 [LIRIC]
Dahbi, Laurence [Auteur]
Equipe NuTox (LNC - U1231) [NUTOX]
Lipides - Nutrition - Cancer [Dijon - U1231] [LNC]
dine, thierry [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - ULR 7365
Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 [GRITA]
Moreau, Emmanuel [Auteur]
Imagerie Moléculaire et Stratégies Théranostiques [IMoST]
Sautou, Valerie [Auteur]
SIGMA Clermont [SIGMA Clermont]
Chagnon, Marie-Christine [Auteur]
Equipe NuTox (LNC - U1231) [NUTOX]
Lipides - Nutrition - Cancer [Dijon - U1231] [LNC]
Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - ULR 7365
Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 [GRITA]
Severin, Isabelle [Auteur]
Equipe NuTox (LNC - U1231) [NUTOX]
Farce, Amaury [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Lille Inflammation Research International Center - U 995 [LIRIC]
Dahbi, Laurence [Auteur]
Equipe NuTox (LNC - U1231) [NUTOX]
Lipides - Nutrition - Cancer [Dijon - U1231] [LNC]
dine, thierry [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - ULR 7365
Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 [GRITA]
Moreau, Emmanuel [Auteur]
Imagerie Moléculaire et Stratégies Théranostiques [IMoST]
Sautou, Valerie [Auteur]
SIGMA Clermont [SIGMA Clermont]
Chagnon, Marie-Christine [Auteur]
Equipe NuTox (LNC - U1231) [NUTOX]
Lipides - Nutrition - Cancer [Dijon - U1231] [LNC]
Journal title :
Metabolites
Abbreviated title :
Metabolites
Volume number :
11
Pages :
94
Publisher :
MDPI
Publication date :
2021-02-10
ISSN :
2218-1989
Keyword(s) :
thyroid receptors
hormonal activities
T-screen assay
DEHT
in silico
hormonal activities
T-screen assay
DEHT
in silico
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
Plasticizers added to polyvinylchloride (PVC) used in medical devices can be released into patients' biological fluids. Di-(2-ethylhexyl)phthalate (DEHP), a well-known reprotoxic and endocrine disruptor, must be replaced ...
Show more >Plasticizers added to polyvinylchloride (PVC) used in medical devices can be released into patients' biological fluids. Di-(2-ethylhexyl)phthalate (DEHP), a well-known reprotoxic and endocrine disruptor, must be replaced by alternative compounds. Di-(2-ethylhexyl) terephthalate (DEHT) is an interesting candidate due to its lower migration from PVC and its lack of reprotoxicity. However, there is still a lack of data to support the safety of its human metabolites with regard to their hormonal properties in the thyroid system. The effects of DEHT metabolites on thyroid/hormone receptors (TRs) were compared in vitro and in silico to those of DEHP. The oxidized metabolites of DEHT had no effect on T3 receptors whereas 5-hydroxy-mono-(ethylhexyl)phthalate (5-OH-MEHP) appeared to be primarily an agonist for TRs above 0.2 µg/mL with a synergistic effect on T3. Monoesters (MEHP and mono-(2-ethylhexyl)terephthalate, MEHT) were also active on T3 receptors. In vitro, MEHP was a partial agonist between 10 and 20 µg/mL. MEHT was an antagonist at non-cytotoxic concentrations (2-5 µg/mL) in a concentration-dependent manner. The results obtained with docking were consistent with those of the T-screen and provide additional information on the preferential affinity of monoesters and 5-OH-MEHP for TRs. This study highlights a lack of interactions between oxidized metabolites and TRs, confirming the interest of DEHT.Show less >
Show more >Plasticizers added to polyvinylchloride (PVC) used in medical devices can be released into patients' biological fluids. Di-(2-ethylhexyl)phthalate (DEHP), a well-known reprotoxic and endocrine disruptor, must be replaced by alternative compounds. Di-(2-ethylhexyl) terephthalate (DEHT) is an interesting candidate due to its lower migration from PVC and its lack of reprotoxicity. However, there is still a lack of data to support the safety of its human metabolites with regard to their hormonal properties in the thyroid system. The effects of DEHT metabolites on thyroid/hormone receptors (TRs) were compared in vitro and in silico to those of DEHP. The oxidized metabolites of DEHT had no effect on T3 receptors whereas 5-hydroxy-mono-(ethylhexyl)phthalate (5-OH-MEHP) appeared to be primarily an agonist for TRs above 0.2 µg/mL with a synergistic effect on T3. Monoesters (MEHP and mono-(2-ethylhexyl)terephthalate, MEHT) were also active on T3 receptors. In vitro, MEHP was a partial agonist between 10 and 20 µg/mL. MEHT was an antagonist at non-cytotoxic concentrations (2-5 µg/mL) in a concentration-dependent manner. The results obtained with docking were consistent with those of the T-screen and provide additional information on the preferential affinity of monoesters and 5-OH-MEHP for TRs. This study highlights a lack of interactions between oxidized metabolites and TRs, confirming the interest of DEHT.Show less >
Language :
Anglais
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
CHU Lille
Inserm
Université de Lille
Inserm
Université de Lille
Collections :
Submission date :
2021-07-06T12:49:57Z
2022-01-19T09:26:45Z
2022-01-26T11:19:13Z
2022-02-02T09:57:19Z
2022-01-19T09:26:45Z
2022-01-26T11:19:13Z
2022-02-02T09:57:19Z