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 by a clinical damage score, colon length, weight loss, stool consistency and rectal bleeding. Inflammatory response was assessed by neutrophil infiltration, determined by histology and myeloperoxidase (MPO) activity. Interleukin (IL)-1 beta, 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-1 beta 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-1 beta and increase of PG production in colon mucosa.
Villegas
Isabel
I
Department of Pharmacology, Faculty of Pharmacy, University of Seville, Calle Profesor García González, 41012 Seville, Spain.
Alarcón de la Lastra
Catalina
C
Orjales
Aurelio
A
La Casa
Carmen
C
D000284:Administration, Oral; D000818:Animals; D003093:Colitis, Ulcerative / Q000139:chemically induced* / Q000188:drug therapy; D044683:Colon, Descending / Q000187:drug effects / Q000293:injuries / Q000648:ultrastructure; D044684:Colon, Transverse / Q000187:drug effects / Q000293:injuries / Q000648:ultrastructure; D016264:Dextran Sulfate / Q000008:administration & dosage / Q000009:adverse effects* / Q000037:antagonists & inhibitors*; D015232:Dinoprostone / Q000096:biosynthesis; D004145:Diosmin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004326:Drinking; D005419:Flavonoids / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D007375:Interleukin-1 / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology / Q000293:injuries; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020556:Neutrophil Infiltration / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D015230:Prostaglandin D2 / Q000096:biosynthesis; D013997:Time Factors; D014867:Water
D005419:Flavonoids; D007375:Interleukin-1; D014867:Water; D004145:Diosmin; D016264:Dextran Sulfate; D009195:Peroxidase; D015232:Dinoprostone; C474240:dosmalfate; D015230:Prostaglandin D2