BENEFICIAL EFFECT OF URSODEOXYCHOLIC ACID ON MUCOSAL DAMAGE IN TRINITROBENZENE SULFONIC ACID-INDUCED COLITIS

Background: Recently we observed that ursodeoxycholic acid (UDCA) amel iorates an experimental small intestinal inflammation induced by indom ethacin in the rat. In this study, we have tested whether ursodeoxycho lic acid also reduces mucosal damage in the bile-independent trinitrob enzene sulphonic acid (TNB) model of experimental colitis. Methods: In testinal inflammation (colitis) was induced in male Sprague-Dawley rat s (250-300 g) by intracolonic administration of TNB (30 mg in 50% etha nol). Rats were treated with UDCA (10 mg/kg) either for 3 days startin g with the administration of TNB for an acute inflammation (n = 11) or for 8 days starting one day after induction of colitis related to a m ore acute/chronic inflammation (n = 11). Rats were sacrificed at day 3 or day 9, respectively. Healing of induced colitis was assessed by ma croscopic and blinded microscopic analysis as well as by measurement o f bowel wet weight, daily body weight, and myeloperoxidase activity. A ll examinations were separately performed in three colon segments (S1 3-5 cm, S2 5.5-8 cm and S3 8.5-11 cm from anus). Results: UDCA treatme nt significantly reduced macroscopically and microscopically detectabl e injury in acute inflammation in segments 1 and 2. The colitis-rats w ith acute/chronic inflammation had less marked mucosal damage. Neverth eless, UDCA treatment led to a significant decrease of visible injury parameters which was seen exclusively at the area of maximal ulceratio n (S2). Furthermore, a significant increase in body weight of UDCA-tre ated TNB rats compared to controls from day 5 on was found. Conclusion : Ursodeoxycholic acid attenuates the severity of acute inflammation a nd inhibits the development of acute/chronic inflammation predominantl y around the area of maximal ulceration in TNB-induced colitis. In add ition to our previous studies and results in indomethacin induced ente ritis, these data may provide a rationale for studying how UDCA modula tes functions of immune cells in the colonic mucosa.