Simvastatin Inhibits Histologic Changes Associated with Gastroduodenal Reflux in a Murine Model.
Dig Dis Sci
; 67(10): 4732-4741, 2022 10.
Article
em En
| MEDLINE
| ID: mdl-35001242
ABSTRACT
BACKGROUND:
Observational studies demonstrate a protective effect of statins on the development and progression of esophageal adenocarcinoma. The role of statins in the prevention of reflux-induced esophageal changes remains unknown.AIMS:
Using a mixed gastroduodenal reflux mouse model, we hypothesized that oral administration of simvastatin would attenuate reflux-induced mucosal changes of the distal esophagus.METHODS:
Human Barrett's (CPB) and esophageal adenocarcinoma (FLO1 and OE19) cells were treated with simvastatin. Cell proliferation and apoptosis were evaluated using the MTS proliferation and annexin V apoptosis assays, respectively. A reflux mouse model was generated by performing a side-to-side anastomosis between the gastroesophageal junction and first portion of the duodenum (duodeno-gastroesophageal anastomosis, DGEA). DGEA mice were fed a standard or simvastatin-containing diet following surgery. Mice were euthanized 6 weeks post-operatively.RESULTS:
Simvastatin significantly decreased proliferation and increased apoptosis in all cell lines. Compared to control animals, mice undergoing DGEA who were fed a standard diet demonstrated a fourfold increase in mucosal thickness and significant increase in proliferating cells (p < 0.0001). DGEA mice fed a simvastatin-containing diet had an attenuated response to reflux, with a significant reduction in mucosal hyperplasia and proliferation (p < 0.0001). DGEA mice fed a simvastatin-containing diet demonstrated significant upregulation of procaspase-3 (p = 0.009) and cleaved caspase-3 (p = 0.034) in the distal esophagus.CONCLUSIONS:
We demonstrate for the first time a reduction in reflux-induced histologic changes of the distal esophagus following oral administration of simvastatin in vivo. These findings identify simvastatin as a potential preventative agent to inhibit the development and progression of reflux-induced esophageal injury.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Esôfago de Barrett
/
Neoplasias Esofágicas
/
Adenocarcinoma
/
Esofagite Péptica
/
Refluxo Gastroesofágico
/
Inibidores de Hidroximetilglutaril-CoA Redutases
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Dig Dis Sci
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos