Rebamipide Enema is Effective for Treatment of Experimental Dextran Sulfate Sodium Induced Colitis in Rats

Abstract

We investigated therapeutic efficacy of rebamipide using dextran sulfate sodium (DSS) induced colitis model in rats. Three percent DSS solution was given to rats for 9 days. After that, we evaluated the drug efficacy on colitis sustained with continuous drinking of 1% DSS. Twice-daily treatment with 0.3% or 1% rebamipide for 14 days significantly ameliorated the stool abnormality in the colitis model, preferentially suppressed hematochezia. The colonic mucosal lesion, determined by Alcian blue staining on day 24, was significantly reduced by rebamipide enema in a dose-dependent manner. Either rebamipide or 5-aminosalycilic acid (5-ASA) enema treated once daily significantly ameliorated colitis. The minimum effective dose of rebamipide was 0.3% in once-daily treatment, and that of 5-ASA was 10%. In a mechanistic study, the epithelial cell sheet formation of the T84 colon cancer cell was measured as an increase in generation of trans-epithelial electrical resistance in vitro. Rebamipide accelerated the increase, while 5-ASA conversely suppressed it. These results suggest that rebamipide enema is effective for treatment of experimental ulcerative colitis (UC).

Prophylactic Effect of Rebamipide on Aspirin-Induced Gastric Lesions and Disruption of Tight Junctional Protein Zonula Occludens-1 Distribution

“…Recently, it was reported that aspirin also disrupted the distribution of ZO-1 proteins in HT-29 cells (65). It is reported that the effect of rebamipide on permeability increase induced by indomethacin is associated with the preservation of trans-epithelial electrical resistance (TEER) in RGM-1 cells (48), and recently, an increasing effect of TEER by rebamipide has been reported in T84 cells (66). However, these effects of rebamipide were not elucidated from the aspect of tight junctional complexes.…”

Effect of rectal administration of rebamipide on dextran sulfate sodium-induced colitis: Role of hepatocyte growth factor

“…Rebamipide prevented DSScolitis through suppressing inflammatory cytokines [8] and myeloperoxidase activity in leukocytes [9]. Recently, intrarectal administration has been to be an effective route of rebamipide [5,10]. Indeed, the efficacy of rebamipide enemas have been reported [6,7].…”

“…Furthermore, rebamipide enema is effective in patients with UC who are corticosteroid-resistant [6,7]. Experimental data suggest that rebamipide is useful for DSS-induced colitis [8,9,10], however, its precise mechanisms remain to be clarified.…”

Ultrasound-mediated gastrointestinal drug delivery

“…Power calculations were carried out on the basis of the enhancement in delivery observed in the pig studies using ultrasound as well as previously published reports examining fecal scores (7). Nosamples were excluded from analysis in this study.…”

“…First-line therapy for the most common IBD subtype, ulcerative colitis, includes aminosalicylates administered orally or rectally, with the latter being recognized as more efficacious, particularly in patients with mild to moderate disease activity (5, 6). However, rectal (enema) treatment efficacy is directly dependent on retention time and tissue absorption of the drug (6, 7), which is challenging for patients suffering from diarrhea with frequent bowel movements. Higher mucosal concentrations of these agents have been shown to correlate with decreased disease activity (6).…”