Melatonin reduces dinitrobenzene sulfonic acid-induced colitis

Inflammatory bowel disease (IBD) is characterized by oxidative and nitrosat ive stress, leukocyte infiltration, and up-regulation of intercellular adhe sion molecule 1 (ICAM-1) expression in the colon. The aim of this study was to examine the effects of the pineal secretory product melatonin in rats s ubjected to experimental colitis. Colitis was induced in rats by intracolon ic instillation of dinitrobenzene sulfonic acid (DNBS). Rats experienced bl oody diarrhea and a significant loss of body weight, Four days after DNBS a dministration, the colon damage was characterized by areas of mucosal necro sis. Neutrophil infiltration (indicated by myeloperoxidase [MPO] activity i n the mucosa) was associated with up-regulation of ICAM-1, expression of P- selectin, and high levels of malondialdehyde (MDA). Immunohistochemistry fo r nitrotyrosine and poly (ADP-ribose) synthetase (PARS) showed an intense s taining in the inflamed colon. Staining of colon tissue sections obtained f rom DNBS-treated rats with an anti-cycloxygenase-2 (COX-2) antibody showed a diffuse staining of the inflamed tissue. Furthermore, expression of induc ible nitric oxide synthase (iNOS) was found mainly in the macrophages of th e inflamed colons from DNBS-treated rats. Treatment with melatonin (15 mg/k g daily, intraperitoneally) significantly reduced the appearance of diarrhe a and the loss of body weight. This was associated with a remarkable amelio ration of the disruption of the colonic architecture, as well as a signific ant reduction of colonic MPO activity and MDA levels. Melatonin also reduce d the appearance of nitrotyrosine and PARS immunoreactivity ill the colon, as well as reducing the up-regulation of ICAM-1 and the expression of P-sel ectin. The intensity and degree of the stainings for COX-2 and iNOS were ma rkedly reduced in tissue sections obtained from melatonin-treated rats. The results of the this study suggest that the administration of melatonin mig ht be beneficial for the treatment of IBD.