bismuth-tripotassium-dicitrate and Colitis

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.

Topics: Animals; Anti-Ulcer Agents; Bismuth; Colitis; Female; Mesalamine; Organometallic Compounds; Rats; Rats, Sprague-Dawley; Salicylates; Trinitrobenzenesulfonic Acid

Colloid bismuth subcitrate (CBS) has a protective effect on ulcerated gastric and duodenal mucosa. To investigate its effect on large intestinal mucosal injury, we used acetic acid-induced colitis in the rat. Colitis was produced in male Wistar rats by rectal instillation of 1 ml of 10% acetic acid followed immediately by 1.5 ml of NaCl 0.9% (saline) enema. 1.5 ml of saline containing 240 mg of CBS or saline alone were then administered rectally every 24 h for 5 days. Another group of animals received CBS only. On the sixth day the distal colon was examined macroscopically and histologically using a 0 (normal) to 3 (necrosis) score. Prostaglandin E2 (PGE2) was measured by RIA (ng/mg protein). CBS significantly reduced both macroscopic and microscopic scores from 2.09 to 1.25 (p < 0.02) and from 2.4 to 1.08 (p < 0.02) respectively. It also induced a significant reduction in PGE2 from 1.6 to 0.57 (p < 0.004) in the inflamed colonic mucosa. The significant protective effect of topical CBS, which is accompanied by a reduction of PGE2, indicates that CBS may have a role in the treatment of colitis.

Topics: Acetates; Acetic Acid; Animals; Bismuth; Colitis; Dinoprostone; Intestinal Mucosa; Male; Organometallic Compounds; Rats; Rats, Wistar