The present study aimed to verify the efficacy of
tranilast (TL) for treating
inflammatory bowel disease (IBD) with the use of an experimental
colitis model. The experimental
colitis model was prepared by intrarectal instillation of 2,4,6-trinitrobenzenesulfonic
acid (TNBS; 40mg/kg) dissolved in water containing 25%
ethanol. The pharmacological effects of TL after repeated
oral administration were evaluated by
biomarker and histological analyses, and the pharmacokinetic behavior of TL was also examined after single
oral administration. The intrarectal instillation of TNBS
solution caused
colitis, as evidenced by ca. 2.2-, 5-, and 3-fold increases in
myeloperoxidase (MPO) activity, infiltrated cell numbers, and the thickness of the submucosa in the colon, respectively. However, orally-taken TL (10mg/kg, twice a day for 9days) led to a 92% reduction in the increase of the MPO level by TNBS
enema, and cellular infiltration and thickened submucosa in the experimental
colitis model tended to also be suppressed by repeated
oral administration of TL. The oral bioavailability of TL in TNBS-treated rats was calculated to be as low as ca. 6.5%, and the poor oral absorption of TL may be a limitation of the treatment for IBD. TL could attenuate TNBS-induced
colitis on the basis of the obtained results, and the anti-inflammatory effects would have clinical relevance to the therapeutic outcomes of TL in IBD patients. Although further improvement in the oral bioavailability of TL might be required for better pharmacological outcomes, TL would be an efficacious agent for treating IBD.