In vitro and in silico approach to study ...
Type de document :
Article dans une revue scientifique: Article original
PMID :
URL permanente :
Titre :
In vitro and in silico approach to study the hormonal activities of the alternative plasticizer tri-(2-ethylhexyl) trimellitate TEHTM and its metabolites.
Auteur(s) :
Dahbi, Laurence [Auteur]
Derttech Packtox
Farce, Amaury [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
KAMBIA, Nicolas [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - ULR 7365
Séverin, Isabelle [Auteur]
Derttech Packtox
dine, thierry [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - ULR 7365
Moreau, Emmanuel [Auteur]
Imagerie Moléculaire et Stratégies Théranostiques [IMoST]
Sautou, Valérie [Auteur]
Institut de Chimie de Clermont-Ferrand [ICCF]
Chagnon, Philippe [Auteur]
Territoires, Villes, Environnement & Société (TVES) - ULR 4477
Derttech Packtox
Farce, Amaury [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
KAMBIA, Nicolas [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - ULR 7365
Séverin, Isabelle [Auteur]
Derttech Packtox
dine, thierry [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - ULR 7365
Moreau, Emmanuel [Auteur]
Imagerie Moléculaire et Stratégies Théranostiques [IMoST]
Sautou, Valérie [Auteur]
Institut de Chimie de Clermont-Ferrand [ICCF]
Chagnon, Philippe [Auteur]
Territoires, Villes, Environnement & Société (TVES) - ULR 4477
Titre de la revue :
Archives of Toxicology
Nom court de la revue :
Arch Toxicol
Numéro :
96
Pagination :
899–918
Éditeur :
Springer Link
Date de publication :
2022-02-04
ISSN :
1432-0738
Mot(s)-clé(s) en anglais :
Medical devices
Steroidogenesis
hER and hAR reporter gene assays
T-screen assay
In silico
TEHTM
Steroidogenesis
hER and hAR reporter gene assays
T-screen assay
In silico
TEHTM
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Résumé en anglais : [en]
Tri-(2-ethylhexyl) trimellitate (TEHTM) is a plasticizer for polyvinyl chloride (PVC) material used in medical devices. It is an alternative to di-(2-ethylhexyl) phthalate (DEHP), a well-known reprotoxic and endocrine ...
Lire la suite >Tri-(2-ethylhexyl) trimellitate (TEHTM) is a plasticizer for polyvinyl chloride (PVC) material used in medical devices. It is an alternative to di-(2-ethylhexyl) phthalate (DEHP), a well-known reprotoxic and endocrine disruptor. As plasticizers are known to easily migrate when in contact with fatty biological fluids, patient exposure to TEHTM is highly probable. However, there is currently no data on the potential endocrine-disrupting effects of its human metabolites. To evaluate the effects of TEHTM metabolites on endocrine activity, they were first synthesized and their effects on estrogen, androgen and thyroid receptors, as well as steroid synthesis, were investigated by combining in vitro and in silico approaches. Among the primary metabolites, only 4-MEHTM (4-mono-(2-ethylhexyl) trimellitate) showed agonist activities on ERs and TRs, while three diesters were TR antagonists at non-cytotoxic concentrations. These results were completed by docking experiments which specified the ER and TR isoforms involved. A mixture of 2/1-MEHTM significantly increased the estradiol level and reduced the testosterone level in H295R cell culture supernatants. The oxidized secondary metabolites of TEHTM had no effect on ER, AR, TR receptors or on steroid hormone synthesis. Among the fourteen metabolites, these data showed that two of them (4-MEHTM and 2/1-MEHTM) induced effect on hormonal activities in vitro. However, by comparing the concentrations of the primary metabolites found in human urine with the active concentrations determined in bioassays, it can be suggested that the metabolites will not be active with regard to estrogen, androgen, thyroid receptors and steroidogenesis-mediated effects.Lire moins >
Lire la suite >Tri-(2-ethylhexyl) trimellitate (TEHTM) is a plasticizer for polyvinyl chloride (PVC) material used in medical devices. It is an alternative to di-(2-ethylhexyl) phthalate (DEHP), a well-known reprotoxic and endocrine disruptor. As plasticizers are known to easily migrate when in contact with fatty biological fluids, patient exposure to TEHTM is highly probable. However, there is currently no data on the potential endocrine-disrupting effects of its human metabolites. To evaluate the effects of TEHTM metabolites on endocrine activity, they were first synthesized and their effects on estrogen, androgen and thyroid receptors, as well as steroid synthesis, were investigated by combining in vitro and in silico approaches. Among the primary metabolites, only 4-MEHTM (4-mono-(2-ethylhexyl) trimellitate) showed agonist activities on ERs and TRs, while three diesters were TR antagonists at non-cytotoxic concentrations. These results were completed by docking experiments which specified the ER and TR isoforms involved. A mixture of 2/1-MEHTM significantly increased the estradiol level and reduced the testosterone level in H295R cell culture supernatants. The oxidized secondary metabolites of TEHTM had no effect on ER, AR, TR receptors or on steroid hormone synthesis. Among the fourteen metabolites, these data showed that two of them (4-MEHTM and 2/1-MEHTM) induced effect on hormonal activities in vitro. However, by comparing the concentrations of the primary metabolites found in human urine with the active concentrations determined in bioassays, it can be suggested that the metabolites will not be active with regard to estrogen, androgen, thyroid receptors and steroidogenesis-mediated effects.Lire moins >
Langue :
Anglais
Audience :
Internationale
Vulgarisation :
Non
Établissement(s) :
Université de Lille
CHU Lille
CHU Lille
Collections :
Date de dépôt :
2023-05-25T02:44:56Z
2023-09-20T07:02:13Z
2023-09-20T07:27:01Z
2023-09-20T07:02:13Z
2023-09-20T07:27:01Z