Abstract | OBJECTIVE AND DESIGN: 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: 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.
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Authors | John J Byrnes, Stefan Gross, Courtney Ellard, Kelly Connolly, Stephen Donahue, Dominic Picarella |
Journal | Inflammation research : official journal of the European Histamine Research Society ... [et al.]
(Inflamm Res)
Vol. 58
Issue 11
Pg. 819-27
(Nov 2009)
ISSN: 1420-908X [Electronic] Switzerland |
PMID | 19517214
(Publication Type: Journal Article)
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Chemical References |
- 2-(1-carboxy-2-(3-(3,5-dichlorobenzyl)-3H-imidazol-4-yl)ethylamino)-4-methylpentanoic acid
- Angiotensin-Converting Enzyme Inhibitors
- Imidazoles
- Dextran Sulfate
- Peroxidase
- Peptidyl-Dipeptidase A
- ACE2 protein, human
- Ace2 protein, mouse
- Angiotensin-Converting Enzyme 2
- Leucine
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Topics |
- Angiotensin-Converting Enzyme 2
- Angiotensin-Converting Enzyme Inhibitors
(therapeutic use)
- Animals
- Body Weight
(drug effects)
- Colitis
(chemically induced, drug therapy, pathology, physiopathology)
- Colon
(enzymology, pathology)
- Dextran Sulfate
(adverse effects)
- Disease Models, Animal
- Female
- Humans
- Imidazoles
(therapeutic use)
- Inflammatory Bowel Diseases
(drug therapy, pathology)
- Leucine
(analogs & derivatives, therapeutic use)
- Mice
- Mice, Inbred BALB C
- Peptidyl-Dipeptidase A
(metabolism)
- Peroxidase
(metabolism)
- Random Allocation
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