Melatonin modulates signal transduction pathways and apoptosis in experimental colitis

Emanuela Mazzon, Emanuela Esposito, Concetta Crisafulli, Luisa Riccardi, Carmelo Muià, Paolo Di Bella, Rosaria Meli, Salvatore Cuzzocrea

Research output: Contribution to journalArticlepeer-review

Abstract

Various evidences have documented that the pineal secretory product melatonin exerts an important anti-inflammatory effect in different experimental models including colitis. The aim of the present study was to evaluate whether melatonin regulates the inflammatory response of experimental colitis in rats at the level of signal transduction pathway. Colitis was induced by intracolonic instillation of dinitrobenzene sulfonic acid (DNBS). Four days after DNBS administration, a substantial increase of colon TNF-α production was associated with the colon damage. In DNBS-treated rats, the colon injury correlated with a significant rise of apoptosis (evaluated by TUNEL coloration) which was associated with a significant increased expression of proapoptotic Bax and decreased colon content of antiapoptotic Bcl-2. This inflammatory response was also related to activation of nuclear factor-κB (NF-κB) and phosphorylation of c-Jun as well as FAS ligand expression in the colon. Treatment with melatonin (15 mg/kg daily i.p.) was associated with a remarkable amelioration of colonic disrupted architecture as well as a significant reduction of TNF-α. Melatonin also reduced the NF-κB activation and phosphorylation of c-Jun as well as the Fas ligand expression in the colon. Furthermore, melatonin reduced the expression of Bax and prevented the loss of Bcl-2 proteins as well as the presence of apoptotic cells caused by DNBS. The results of this study show that melatonin administration exerts beneficial effects in inflammatory bowel disease by modulating signal transduction pathways.

Original languageEnglish
Pages (from-to)363-373
Number of pages11
JournalJournal of Pineal Research
Volume41
Issue number4
DOIs
Publication statusPublished - Nov 2006

Keywords

  • Apoptosis
  • Colon damage
  • DNBS
  • Free radicals
  • Inflammation

ASJC Scopus subject areas

  • Endocrinology

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