Thalidomide treatment reduces the alteration of paracellular barrier function in mice ileum during experimental colitis.
Small intestine permeability is frequently altered in inflammatory bowel diseases and may be caused by the translocation of intestinal toxins through leaky small intestine tight junctions (TJs) and adherence. Thus, the aim of the present study was to examine the effects of thalidomide treatment on the permeability and structure of small intestine TJs in an animal model of experimental colitis induced by dinitrobenzene sulfonic acid (DNBS). Four days after colitis induction with DNBS, the ileal TJs were studied by means of transmission electron microscopy using lanthanum nitrate and immunohistochemistry of occludin and zonula occludens 1. When compared with DNBS-treated mice, thalidomide-treated (200 mg/kg orally starting 30 min after the administration of DNBS) mice subjected to DNBS-induced colitis experienced a significantly reduced rate of the extent and severity of the histological signs of colon injury associated with a significant reduction of plasma and colon tumor necrosis factor alpha levels. After administration of DNBS to the mice induced a significant increase of ileal permeability was observed. Distal colitis in mice induced an increase of TJ permeability throughout the entire small intestine, and the extent of alterations correlates with colonic damage. In particular, we have observed that thalidomide treatment resulted in a significant reduction of the following: (1) the degree of colon injury, (2) the alteration of zonula occludens 1 and occludin localization (immunohistochemistry), and (3) intestinal permeability caused by DNBS in the colon. Taken together, our results clearly show that thalidomide treatment reduced small intestinal permeability in experimental colitis through the regulation of TJ protein.
Mazzon
Emanuela
E
Department Clinical and Experimental Medicine and Pharmacology, University of Messina Torre Biologica, Policlinico Universitario, 98123 Messina, Italy.
Cuzzocrea
Salvatore
S