Melatonin reduces dinitrobenzene sulfonic acid-induced colitis

Salvatore Cuzzocrea, Emanuela Mazzon, Ivana Serraino, Valeria Lepore, Maria Luisa Terranova, Antonio Ciccolo, Achille P. Caputi

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Abstract

Inflammatory bowel disease (IBD) is characterized by oxidative and nitrosative stress, leukocyte infiltration, and up-regulation of intercellular adhesion 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 subjected to experimental colitis. Colitis was induced in rats by intracolonic instillation of dinitrobenzene sulfonic acid (DNBS). Rats experienced bloody diarrhea and a significant loss of body weight. Four days after DNBS administration, the colon damage was characterized by areas of mucosal necrosis. Neutrophil infiltration (indicated by myeloperoxidase [MPO] activity in the mucosa) was associated with up-regulation of ICAM-1, expression of P-selectin, and high levels of malondialdehyde (MDA). Immunohistochemistry for nitrotyrosine and poly (ADP-ribose) synthetase (PARS) showed an intense staining in the inflamed colon. Staining of colon tissue sections obtained from DNBS-treated rats with an anti-cycloxygenase-2 (COX-2) antibody showed a diffuse staining of the inflamed tissue. Furthermore, expression of inducible nitric oxide synthase (iNOS) was found mainly in the macrophages of the inflamed colons from DNBS-treated rats. Treatment with melatonin (15 mg/kg daily, intraperitoneally) significantly reduced the appearance of diarrhea and the loss of body weight. This was associated with a remarkable amelioration of the disruption of the colonic architecture, as well as a significant reduction of colonic MPO activity and MDA levels. Melatonin also reduced the appearance of nitrotyrosine and PARS immunoreactivity in the colon, as well as reducing the up-regulation of ICAM-1 and the expression of P-selectin. The intensity and degree of the stainings for COX-2 and iNOS were markedly reduced in tissue sections obtained from melatonin-treated rats. The results of the this study suggest that the administration of melatonin might be beneficial for the treatment of IBD.

Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalJournal of Pineal Research
Volume30
Issue number1
DOIs
Publication statusPublished - 2001

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Keywords

  • Colon damage
  • Dinitrobenzene sulfonic acid (DNBS)
  • Free radicals
  • Inflammation
  • Nitric oxide
  • Peroxynitrite
  • Poly (ADP-ribose) synthetase (PARS)

ASJC Scopus subject areas

  • Endocrinology

Cite this

Cuzzocrea, S., Mazzon, E., Serraino, I., Lepore, V., Terranova, M. L., Ciccolo, A., & Caputi, A. P. (2001). Melatonin reduces dinitrobenzene sulfonic acid-induced colitis. Journal of Pineal Research, 30(1), 1-12. https://doi.org/10.1034/j.1600-079X.2001.300101.x