Phthalates and non-phthalates plasticizers disrupt lipid metabolism
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Notice bibliographique
Résumé
Plasticizers are synthetic organic chemicals that are used in different products to make them flexible, elastic, and durable. Plasticizers are not attached to the products by covalent bonds, as a result, they leach out from the products leading to environmental contamination. The most widely used plasticizer, Di-(2-ethyl hexyl) phthalate (DEHP), have been restricted from general use in the EU, Canada, and the USA due to their reported toxicity. The alternative plasticizer, Di-(isononyl) cyclohexane-1,2-dicarboxylate (DINCH), was introduced to the European market as a safer alternative for endocrine-disrupting phthalates such as DEHP, and diisononyl phthalate (DINP). According to the current toxicological data, DINCH is neither an endocrine disruptor and nor a reproductive toxicant. Thus, DINCH was approved for use in food contact containers, and in children’s toys. The increase in global demand for alternative plasticizers led to their buildup in the environment and an increase in DINCH exposure. The lack of toxicity data and safety assessment of DINCH has raised the concern to human and animal health. Due to the similar structure of DEHP, DINP, and DINCH, we suggest that DINCH can be classified as a metabolic disruptor that alters fat metabolism and induces adipogenesis. In this study, we investigated the negatives effects of DINCH (at concentrations ranging from 0.01 to 10 μM) compared it to phthalates DINP, DEHP, Dibutyl phthalate (DBP), and Diethyl phthalate (DEP) at the early developmental stages of zebrafish. We further analyzed DINCH and DINP using the mouse preadipocyte cells 3T3L1. We found that DINCH and DEHP caused hatching delay in a dose-dependent manner. Behavioral analysis of larvae demonstrated that DEHP, DBP, DEP, and DINCH impair motor activity. The Oil Red O lipid staining showed a slight lipid accumulation in larval zebrafish at different DINP and DINCH concentrations. To further confirm the findings, qPCR was performed to analyze lipid metabolism genes. DINCH and DINP altered lipid metabolism genes including, fasn, srebp, pparg etc. The oxidative stress state imposed by DINCH exposure was shown by a slight increase in superoxide dismutase enzymatic activity and the alteration on stress-related genes. In 3T3L1 cells, 10 and 100 μM of DINCH and DINP exposure induced lipid droplets formation like that induced by 100 nM rosiglitazone. Genes associated with lipid metabolism and lipid transport were altered by DINCH and DINP. These results indicate that DINCH exposure could induce physiological and metabolic toxicity. The data presented in this thesis could provide crucial information for further toxicological assessment.
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Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,001 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,002 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découle