A new flavonoid derivative, dosmalfate, attenuates the development of dextran sulphate sodium-induced colitis in mice

In this study, we have evaluated the efficacy of dosmalfate, a new flavonoid derivative compound, for the prevention and treatment of experimental colitis. To induce colitis, BALB/c mice received 5% dextran sulphate sodium (DSS) in their drinking water continuously for 7 days. Colitis was quantified...

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Veröffentlicht in:International immunopharmacology 2003-12, Vol.3 (13), p.1731-1741
Hauptverfasser: Villegas, Isabel, Alarcón de la Lastra, Catalina, Orjales, Aurelio, La Casa, Carmen
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Sprache:eng
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Zusammenfassung:In this study, we have evaluated the efficacy of dosmalfate, a new flavonoid derivative compound, for the prevention and treatment of experimental colitis. To induce colitis, BALB/c mice received 5% dextran sulphate sodium (DSS) in their drinking water continuously for 7 days. Colitis was quantified by a clinical damage score, colon lenght, weight loss, stool consistency and rectal bleeding. Inflammatory response was assessed by neutrophil infiltration, determined by histology and myeloperoxidase (MPO) activity. Interleukin (IL)-1β, prostaglandins (PG)E 2 and (PG)D 2 concentrations in colonic tissue, histological and histochemical analysis of the lesions were also measured. Dosmalfate (400–800 mg/kg body weight, p.o.) ameliorated severe colitis reduced the degree of inflammation through reduction of neutrophil infiltration and IL-1β levels. (PG)E 2 and (PG)D 2 synthesis were significantly reduced in colitis control group and treatment with dosmalfate abolished the decrease in PG synthesis in colon mucosa. We conclude that dosmalfate is protective in acute DSS-induced colitis. The beneficial effects seem to be related to a decrease of neutrophil infiltration, absence of up-regulation of IL-1β and increase of PG production in colon mucosa.
ISSN:1567-5769
1878-1705
DOI:10.1016/j.intimp.2003.07.002