Effects of the ACE2 inhibitor GL1001 on acute dextran sodium sulfate-induced colitis in mice.
Inflamm Res
; 58(11): 819-27, 2009 Nov.
Article
en En
| MEDLINE
| ID: mdl-19517214
ABSTRACT
OBJECTIVE AND DESIGN:
Angiotensin-converting enzyme 2 (ACE2) is expressed in gastrointestinal tissue. Previous studies of GL1001, a potent and selective ACE2 inhibitor, have revealed anti-inflammatory activity in the mouse digestive tract. We hypothesized that GL1001 might also produce beneficial effects in a mouse DSS model of inflammatory bowel disease. MATERIALS Female mice were used for study. TREATMENT Animals were treated for 5 days with 5% DSS in the drinking water to induce colitis. For the following 9 days, animals were treated twice daily with GL1001 (30, 100, 300 mg/kg, s.c.), sulfasalazine (150 mg/kg, p.o.), or vehicle.METHODS:
Throughout the experiment, body weight, rectal prolapse, stool consistency, and fecal occult blood were monitored. At termination, colon length, histopathology, and myeloperoxidase activity were assessed.RESULTS:
High-dose GL1001 ameliorated DSS-induced disease activity, including rectal prolapse and intestinal bleeding. The most robust effect of GL1001 was observed 48-96 h post DSS treatment and was comparable in magnitude to that of sulfasalazine. Colon pathology and myeloperoxidase activity were also markedly attenuated by high-dose GL1001 treatment, with the most profound effects observed in the distal segment.CONCLUSIONS:
The findings support the previously observed anti-inflammatory effects of ACE2 inhibition in gastrointestinal tissue and suggest that GL1001 may have therapeutic utility for inflammatory bowel disease.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Inhibidores de la Enzima Convertidora de Angiotensina
/
Sulfato de Dextran
/
Colitis
/
Imidazoles
/
Leucina
Tipo de estudio:
Clinical_trials
/
Prognostic_studies
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Inflamm Res
Asunto de la revista:
ALERGIA E IMUNOLOGIA
/
PATOLOGIA
Año:
2009
Tipo del documento:
Article
País de afiliación:
Estados Unidos