Low-dose hydralazine reduces albuminuria and glomerulosclerosis in a mouse model of obesity-related chronic kidney disease.
Diabetes Obes Metab
; 24(10): 1939-1949, 2022 10.
Article
en En
| MEDLINE
| ID: mdl-35635331
ABSTRACT
AIM:
To determine, using a mouse model of obesity, whether low-dose hydralazine prevents obesity-related chronic kidney disease (CKD).METHODS:
From 8 weeks of age, male C57BL/6 mice received a high-fat diet (HFD) or chow, with or without low-dose hydralazine (25 mg/L) in drinking water, for 24 weeks. Biometric and metabolic variables, renal function and structural changes, renal global DNA methylation, DNA methylation profile and markers of renal fibrosis, injury, inflammation and oxidative stress were assessed.RESULTS:
The HFD-fed mice developed obesity, with glucose intolerance, hyperinsulinaemia and dyslipidaemia. Obesity increased albuminuria and glomerulosclerosis, which were significantly ameliorated by low-dose hydralazine in the absence of a blood pressure-lowering effect. Obesity increased renal global DNA methylation and this was attenuated by low-dose hydralazine. HFD-induced changes in methylation of individual loci were also significantly reversed by low-dose hydralazine. Obese mice demonstrated increased markers of kidney fibrosis, inflammation and oxidative stress, but these markers were not significantly improved by hydralazine.CONCLUSION:
Low-dose hydralazine ameliorated HFD-induced albuminuria and glomerulosclerosis, independent of alterations in biometric and metabolic variables or blood pressure regulation. Although the precise mechanism of renoprotection in obesity is unclear, an epigenetic basis may be implicated. These data support repurposing hydralazine as a novel therapy to prevent CKD progression in obese patients.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Albuminuria
/
Insuficiencia Renal Crónica
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Diabetes Obes Metab
Asunto de la revista:
ENDOCRINOLOGIA
/
METABOLISMO
Año:
2022
Tipo del documento:
Article
País de afiliación:
Australia