Atorvastatin does not ameliorate lithium‐induced nephrogenic diabetes insipidus in mice
Notice bibliographique
Résumé
Lithium (Li) is an important mood‐stabilizing drug used in the treatment of affective disorders. However, as a significant adverse effect patients can develop Nephrogenic Diabetes Insipidus (NDI). NDI is characterized by the inability of the kidney to concentrate urine in response to vasopressin, resulting in severe polyuria and an increased long‐term risk of chronic kidney disease. Li‐NDI is associated with downregulation of the water channel AQP2 and a cellular remodeling of the kidney collecting duct. Effective and safe treatment of Li‐NDI is still lacking. Statins are cholesterol‐lowering drugs, which appear to increase AQP2 membrane‐translocation and improve urine concentration ability in other NDI models. This project will investigate if atorvastatin is able to prevent the Li‐induced changes in mice using a mouse cortical collecting duct cell line (mCCD) and C57BL/6 mice. Biotinylation assays showed that acute (1hr) treatment with simvastatin (p<0.05) or fluvastatin (p<0.0001) increased AQP2 membrane accumulation compared to controls in the mCCD cells. This confirms that the mCCD cell line respond to acute statin treatment as shown before for these two statins in other cellular and animal models. In order to see whether chronic statin treatment abolish the effects of Li, cells were treated with Li and Li/atorvastatin for 48 hrs. Li reduced total AQP2 levels (p<0.01) compared to controls as expected, but combined Li/atorvastatin treatment did not prevent the Li‐induced downregulation of AQP2. Chronic (21 days) Li treatment of mice increased urine output (p<0.0001) and reduced urine osmolality (p<0.0001) compared to controls (receiving normal food). Atorvastatin (given in combination with Li for 21 days) decreased levels of triglycerides in the blood (p<0.05) compared to controls. Combined Li/atorvastatin treatment did not prevent the effects of Li on urine output and urine osmolality. In kidney inner medulla, western blotting showed that Li reduced total AQP2 levels (p<0.001) and increased pS261‐AQP2 levels (p<0.05), and further showed a tendency to pERK1/2 upregulation (p=0.06) compared to controls as shown previously. However, combined Li/atorvastatin treatment did not abolish any of these changes. Immunohistochemistry further showed that atorvastatin did not prevent the Li‐induced increase in intercalated cells and increased proliferation in the inner medulla. In conclusion, both chronic in vitro and in vivo experiments showed that atorvastatin does not appear to have positive effects on prevention of Li‐NDI in mice. Support or Funding Information Danish Medical Research Council, Beckett Fonden, Aase and Ejnar Danielsens Fonden, Knud and Edith Eriksens Mindefond This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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 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 | 0,000 |
| 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) | 0,000 | 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 découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, 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 ».