Selenide stimulates the biliary excretion of arsenic in human HepaRG cells
Notice bibliographique
Résumé
Arsenic is classified by the International Agency for Research on Cancer as a Group I (proven) human carcinogen causing lung, skin and bladder cancer. Conservative estimates suggest that between 92‐220 million people worldwide are exposed to arsenic at levels exceeding the World Health Organization guideline of 10 µg/L. In animal models arsenic and selenium are mutually protective via the formation and biliary excretion of the seleno‐bis (S‐glutathionyl) arsinium ion [SeAs(GS) 2 ] ‐ , which allows for the fecal elimination of both compounds. Consistent with this, selenium deficiency in humans living in arsenic endemic regions is associated with an increased risk of arsenic induced disease. These observations have led to the initiation of human selenium supplementation trials. Despite these ongoing trials in arsenic endemic regions, the influence of selenium on human hepatic handling of arsenic is not adequately understood. Furthermore, supplementation trials have utilized different chemical forms of selenium with unknown influence on efficacy. In the liver, multidrug resistance protein 2 (MRP2/ABCC2) transports arsenic metabolites, including [SeAs(GS) 2 ] ‐ into bile, and the related MRP4 (ABCC4) transports other arsenic metabolites into hepatic sinusoids. We hypothesized that selenium increases biliary excretion of arsenite (As III ) from HepaRG cells, an immortalized cell line used as a surrogate for primary human hepatocytes. Our objective was to study the influence of selenite (Se IV ), selenide (HSe ‐ ), methylselenocysteine (MeSeCys) and selenomethionine (SeMet) on arsenic efflux from HepaRG cells. HepaRG cells were untreated, or treated with 1 µM As III ± selenium (Se IV , HSe ‐ , MeSeCys or SeMet) for 48 hr. Then crude membrane preparations of HepaRG cells were subjected to immunoblots to evaluate the presence of MRP2 and MRP4 proteins. MRP2 function was evaluated by 5(6)‐carboxy,2’,7’ dichlorofluorescein (CDF) accumulation in canalicular networks by fluorescence microscopy. Transport across sinusoidal and canalicular membranes was measured after treatment of HepaRG cells with 1 µM 73 As III ± selenium (Se IV , HSe ‐ , MeSeCys or SeMet) using B‐CLEAR® technology. Biliary excretion indices (BEIs) were calculated to quantify the extent of arsenic export into bile. Transport was re‐evaluated under conditions expected to inhibit efflux. MRP2 and MRP4 proteins are present in HepaRG cells. MRP2 levels increased after treatment with As III ± HSe ‐ , whereas MRP4 levels increased after treatment with 1 µM As III . CDF accumulated in canalicular networks, suggesting the presence of functional MRP2. At a 5 minute time point, the BEI of 73 As III alone was 13±7%, which was stimulated by the presence of HSe ‐ (BEI=31±7%). Biliary excretion of 73 As III was lost in the presence of other selenium forms, but sinusoidal efflux of 73 As III was stimulated by MeSeCys. Reduction of hepatobiliary transport was observed at 4 ∘ C as well as with inhibitors of glutathione synthesis and MRPs. Arsenic underwent biliary excretion in HepaRG cells, and this was stimulated by HSe ‐ , the biologically active form of selenium metabolism. Arsenic hepatobiliary transport by MRP2 is temperature and glutathione dependent. This work advances understanding of selenium effects on arsenic handling by human liver.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,001 |
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 découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».