Vildagliptin Treatment Ameliorates Renal Interstitial Fibrosis in a Murine Model of Unilateral Ureteral Obstruction.
Biol Pharm Bull
; 47(1): 37-42, 2024.
Article
em En
| MEDLINE
| ID: mdl-38171778
ABSTRACT
Renal interstitial fibrosis in mice can be modeled using unilateral ureteral obstruction (UUO). Here, we investigated the anti-fibrotic effects of the dipeptidyl peptidase-4 inhibitor vildagliptin in this model. We found that vildagliptin given in the drinking water at 10.6 ± 1.5 mg/kg/d prevented fibrosis. Mechanistically, UUO was associated with extracellular signal-regulated kinase (ERK) phosphorylation and with the accumulation of the toxic lipid peroxidation product expression of 4-hydroxy-2-nonenal (4-HNE). Both were significantly inhibited by vildagliptin. Similarly, UUO caused reductions in heme oxygenase-1 (HO-1) mRNA in the kidney, whereas interleukin-6 (IL-6) and cyclooxygenase-1 (COX-1) mRNA were increased; these effects were also prevented by vildagliptin. Taking these data together, we propose that vildagliptin reduces renal interstitial fibrosis resulting from UUO by means of its effects on ERK phosphorylation and the amounts of 4-HNE, HO-1, IL-6 and COX-1 in the kidney.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Obstrução Ureteral
/
Nefropatias
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Biol Pharm Bull
Assunto da revista:
BIOQUIMICA
/
FARMACOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article