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

The 2,4,6-trinitrobenzene sulfonic acid (TNBS) -induced model of chronic inflammation of the rat colon was used to determine the efficacy of bismuth subsalicylate (BSS), bismuth subcitrate (CBS), and 5-aminosalicylic acid (5-ASA) administered in enema form. A novel bismuth compound 1, 2-bis[2-(1,3-dithiobismolane)thio]ethane [Bi2(EDT)3] was also tested. On day 1 colitis was induced with 50 mg TNBS/50% ethanol in female Sprague-Dawley rats, while controls received a saline enema. On day 3, twice-daily treatment with enemas of either saline, BSS, CBS, Bi2(EDT)3, or 5-ASA were initiated in the colitis and control rats. All rats were killed on day 14, and the colons excised, weighed, rated macroscopically, and then fixed for hematoxylin and eosin staining. Blinded microscopic scoring was used to determine injury and healing in all groups. Colon mass and macroscopic scores were increased (P < 0.05) in the group of rats treated with TNBS (N = 16) compared to saline controls (N = 12). Colon mass and macroscopic scores in controls treated with BSS (N = 4), CBS (N = 4), Bi2(EDT)3 (N = 4), and 5-ASA (N = 4) alone 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 Bi2(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-Wallis) 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 treated with TNBS plus saline. It appeared that Bi2(EDT)3 was not protective against injury at the microscopic level but that the novel Bi2(EDT)3 has 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.