Benefit of combination therapy with dapagliflozin and eplerenone on cardiac function and fibrosis in rats with non-diabetic chronic kidney disease.

Animals Glucosides / pharmacology Benzhydryl Compounds / pharmacology Fibrosis Renal Insufficiency, Chronic / drug therapy Eplerenone / pharmacology Rats Male Drug Therapy, Combination Disease Models, Animal Sodium-Glucose Transporter 2 Inhibitors / pharmacology Heart / drug effects Mineralocorticoid Receptor Antagonists / pharmacology Kidney / drug effects Rats, Sprague-Dawley
5/6 nephrectomy Cardiorenal Chronic kidney disease Mineralocorticoid receptor antagonist Sodium-glucose cotransporter-2 inhibitor

Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
14 Oct 2024
Historique:
received: 29 04 2024
accepted: 30 09 2024
medline: 14 10 2024
pubmed: 14 10 2024
entrez: 13 10 2024
Statut: epublish

Résumé

Patients with chronic kidney disease (CKD) are at a high risk of cardiovascular (CV) complications. In these patients, sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been shown to reduce CV events. Mineralocorticoid receptor antagonists (MRAs) exert similar benefits in diabetic CKD, though their effects in non-diabetic CKD remain unclear. This study aimed to evaluated whether the combination of Dapagliflozin (DAPA) and Eplerenone (EPLE) would have positive effects on cardiorenal functions in a non-diabetic CKD model. CKD was induced in rats via 5/6 nephrectomy, followed by treatment with DAPA (5 mg/kg/day PO), EPLE (100 mg/kg/day PO) or the combination for 3 months following CKD induction. Cardiorenal functions were assessed after the treatment period. All treated groups showed reduced kidney fibrosis though plasma creatinine and urea levels remained unchanged. Compared to untreated CKD, EPLE or DAPA/EPLE reduced left ventricle (LV) end-diastolic pressure and LV end-diastolic pressure volume relationship, whereas DAPA alone did not achieve significant reductions. Compared to untreated CKD, EPLE and DAPA/EPLE improved cardiac perfusion but DAPA alone did not. Cardiac fibrosis in CKD was blunted by either DAPA or EPLE alone, with the combination showing an additive effect. In conclusion, co-treatment with DAPA and EPLE enhances diastolic function, cardiac perfusion and reduces myocardial fibrosis in non-diabetic CKD rats.

Identifiants

DOI: 10.1038/s41598-024-74934-z PMID: 39397161
pubmed: 39397161
doi: 10.1038/s41598-024-74934-z
pii: 10.1038/s41598-024-74934-z
doi:

Substances chimiques

Glucosides 0
dapagliflozin 1ULL0QJ8UC
Benzhydryl Compounds 0
Eplerenone 6995V82D0B
Sodium-Glucose Transporter 2 Inhibitors 0
Mineralocorticoid Receptor Antagonists 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

23955

Subventions

Organisme : Agence Nationale de la Recherche
ID : ANR-15-RHUS-0004

Informations de copyright

© 2024. The Author(s).

Références

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Auteurs

M Soulié (M)

INSERM, UMRS 1138, Centre de Recherche des Cordeliers, Sorbonne Université, Université Paris Cité, Paris, France.
INSERM U1096, Normandie Univ, UNIROUEN, Rouen, France.

Y Stephan (Y)

INSERM U1096, Normandie Univ, UNIROUEN, Rouen, France.

M Durand (M)

INSERM, UMRS 1138, Centre de Recherche des Cordeliers, Sorbonne Université, Université Paris Cité, Paris, France.

I Lima-Posada (I)

INSERM, UMRS 1138, Centre de Recherche des Cordeliers, Sorbonne Université, Université Paris Cité, Paris, France.

R Palacios-Ramírez (R)

INSERM, UMRS 1138, Centre de Recherche des Cordeliers, Sorbonne Université, Université Paris Cité, Paris, France.

L Nicol (L)

INSERM U1096, Normandie Univ, UNIROUEN, Rouen, France.

N Lopez-Andres (N)

Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigación Sanitaria de Navarra (IdiSNA), Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA), Pamplona, Spain.

P Mulder (P)

INSERM U1096, Normandie Univ, UNIROUEN, Rouen, France.

F Jaisser (F)

INSERM, UMRS 1138, Centre de Recherche des Cordeliers, Sorbonne Université, Université Paris Cité, Paris, France. frederic.jaisser@inserm.fr.
INSERM Centre d'Investigations Cliniques-Plurithématique 1433, UMR 1116, CHRU de Nancy, French-Clinical Research Infrastructure Network (F-CRIN) INI-CRCT, Université de Lorraine, Nancy, France. frederic.jaisser@inserm.fr.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Benefit of combination therapy with...
questionsmedicales.fr › Glucides › Hétérosides › Glucosides › Benefit of combination therapy with...
questionsmedicales.fr › Composés chimiques organiques › Hydrocarbures › Hydrocarbures cycliques › Hydrocarbures aromatiques › Dérivés du benzène › Composés benzhydryliques › Benefit of combination therapy with...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Fibrose › Benefit of combination therapy with...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Maladie chronique › Insuffisance rénale chronique › Benefit of combination therapy with...
questionsmedicales.fr › Composés polycycliques › Composés à cycles fusionnés › Stéroïdes › Prégnanes › Prégnènes › Éplérénone › Benefit of combination therapy with...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Rats › Benefit of combination therapy with...
questionsmedicales.fr › Thérapeutique › Traitement médicamenteux › Association de médicaments › Benefit of combination therapy with...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › Benefit of combination therapy with...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Effets physiologiques des médicaments › Hypoglycémiants › Inhibiteurs du cotransporteur sodium-glucose de type 2 › Benefit of combination therapy with...
questionsmedicales.fr › Système cardiovasculaire › Coeur › Benefit of combination therapy with...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Effets physiologiques des médicaments › Diurétiques › Diurétiques d'épargne potassique › Antagonistes des récepteurs des minéralocorticoïdes › Benefit of combination therapy with...
questionsmedicales.fr › Appareil urogénital › Voies urinaires › Rein › Benefit of combination therapy with...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Rats › Rat Sprague-Dawley › Benefit of combination therapy with...