Activated neutrophils and proinflammatory
cytokines, such as
tumor necrosis factor-alpha (
TNF-alpha) are clearly involved in the pathogenesis of bowel disease. Increased expression of
epidermal growth factor-receptor (
EGF receptor) has been reported for the colon mucosa surrounding areas of ulceration, suggesting a pivotal role in mucosal defence and repair. In this study, we examined the effects of
dosmalfate, a new
flavonoid derivative compound (
diosmin heptakis) with
antioxidant and cytoprotective properties, on acute and chronic experimental trinitrobenzene sulphonic
acid (TNBS)-induced
colitis in rats. The
inflammation response was assessed by neutrophil infiltration as evaluated by histology and
myeloperoxidase activity. Mucosal
TNF-alpha production and histological analysis of the lesions was also carried out. In addition, we studied the expression of the
EGF receptor inmunohistochemically during the healing of TNBS-induced chronic
colitis. A 2-day treatment with 400 or 800 mg/kg of
dosmalfate ameliorated the colon damage score and the incidence of adhesions. It also significantly (P<0.05) decreased
myeloperoxidase activity and colonic mucosal production of
TNF-alpha. Chronic treatment (14 days) with 800 mg/kg/day of
dosmalfate also had significant protective effects on TNBS-induced
colitis which were reflected by significant attenuation (P<0.05) of the damage score while the inflammatory indicators were not improved. The chronic beneficial effect of
dosmalfate was apparently related to the enhancement of
EGF receptor expression. These findings confirm the protective effects of
dosmalfate in acute and chronic experimental
colitis.