Amelioration of experimental colitis by thalidomide

• Published in: The Israel Medical Association journal Vol. 3; no. 9; p. 644
• Main Authors: Kenet, G, Wardi, J, Avni, Y, Aeed, H, Shirin, H, Zaidel, L, Hershkoviz, R, Bruck, R
• Format: Journal Article
• Language: English
• Published: Israel 01.09.2001
• Subjects: Alkylating Agents - toxicity; Animals; Colitis - chemically induced; Colitis - drug therapy; Colitis - pathology; Immunosuppressive Agents - therapeutic use; Iodoacetamide - toxicity; Rats; Thalidomide - therapeutic use; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 1565-1088

Rectal administration of iodoacetamide induces colitis by blocking sulphhydryl groups and generating inflammatory mediators. Thalidomide, a non-barbiturate hypnotic, also has an anti-inflammatory effect, presumably by suppressing the production of tumor necrosis factor alpha. In patients with Crohn's disease, neutralization or suppression of TNF alpha reduces inflammation. To evaluate the effects of thalidomide in a model of experimental colitis. Colitis was induced in rats by intracolonic administration of 3% iodoacetamide. In the treatment group, thalidomide 50 mg/kg was given daily by gavage and continued for 7 days until the rats were sacrificed. Their colons were then processed for wet weight, lesion area, weight of mucosal scraping, myeloperoxidase activity and histology. Serum levels of TNF were determined. Colonic wet weight, lesion area, myeloperoxidase activity and serum levels of TNF alpha were significantly lower (P < 0.05) in the treatment group (iodoacetamide + thalidomide) than the control group (iodoacetamide only). Histologically, colonic inflammation in the treated group was markedly decreased. Thalidomide effectively decreases colitis induced by iodoacetamide. The mechanism is probably associated with inhibition of TNF alpha, and should be further studied.