Therapeutic role for bismuth compounds in TNBS-induced colitis in the rat

The 2,4,6-trinitrobenzene sulfonic acid (TNBS) -induced model of chronic in flammation of the rat colon was used to determine the efficacy of bismuth s ubsalicylate (BSS)? bismuth subcitrate (CBS), and 5-aminosalicylic acid (5- ASA) administered in enema form. A novel bismuth compound 1, 2-bis[2-(1,3-d ithiobismolane)thio]ethane [Bi-2(EDT)(3)] was also tested. On day 1 colitis was induced with 50 mg TNBS/50% ethanol in female Sprague-Dawley rats, whi le controls received a saline enema. On day 3, twice-daily treatment with e nemas of either saline, BSS, CBS, Bi-2(EDT)(3), or 5-ASA were initiated in the colitis and control rats. All rats were killed on day 14, and the colon s excised, weighed, rated macroscopically, and then fixed for hematoxylin a nd eosin staining. Blinded microscopic scoring was used to determine injury and healing in all groups. Colon mass and macroscopic scores were increase d (P < 0.05) in the group of rats treated with TNBS (N = 16) compared to sa line controls (N = 12), Colon mass and macroscopic scores in controls treat ed with BSS (N = 4), CBS (N = 4), Bi-2(EDT)(3) (N = 4) and 5-ASA (N = 4) al one did not differ from saline control animals. Macroscopic scoring showed a decrease (P < 0.05) in the degree of damage in the group of rats treated with TNBS plus BSS (N = 15), TNBS plus Bi-2(EDT)(3) (N = 10) and TNBS plus CBS (N = 4) compared to the group of rats treated with TNBS plus saline (N = 16). A decrease (P < 0.05) in injury and an increase (P < 0.05, Kruskal-W allis) in healing was observed in the groups of rats treated with TNBS plus BSS, TNBS plus CBS, and TNBS plus 5-ASA compared to the group of rats trea ted with TNBS plus saline. It appeared that Bi-2(EDT)(3) was not protective against injury at the microscopic level but that the novel Bi-2(EDT)(3) ha s an effective healing capacity at the macroscopic level. We conclude that BSS and CBS decrease injury and/or promote healing as effectively as 5-ASA in this model.