Chronic lithium administration ameliorates 2,4,6-trinitrobenzene sulfonic acid-induced colitis in rats; potential role for adenosine triphosphate sensitive potassium channels

Ali Daneshmand, Hamed Mohammadi, Reza Rahimian, Peiman Habibollahi, Gohar Fakhfouri, Saman Shafat Talab, Shahram Ejtemaei Mehr, Ahmad Reza Dehpour

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Background and Aim: Inflammatory bowel disease (IBD) is a multi-factorial disease with an unknown etiology characterized by oxidative stress, leukocyte infiltration and a rise in inflammatory cytokines. This study was conducted to investigate lithium in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced chronic model of experimental IBD, and the contribution of potassium channels as a possible underlying mechanism. Methods: Experimental IBD was induced in rats by a single colonic administration of 10mg of TNBS. Lithium, Glibenclamide (a potassium channel blocker), Lithium+Glibenclamide, Cromakalim or Lithium+Glibenclamide+Cromakalim were given twice daily for 7 successive days. At the end of the experiment, macroscopic and histopathologic scores, colonic malondialdehyde (MDA), tumor necrosis factor-α (TNF-α) level, and myeloperoxidase (MPO) activity as well as plasma lithium level were assessed. Results: Both macroscopic and histological features of colonic injury were markedly ameliorated by lithium. Likewise, the elevated amounts of MPO and MDA were diminished as well as those of TNF-α (P<0.05). Glibenclamide reversed the effect of lithium on these markers, Addition of cromakalim abrogated the effects mediated by glibenclamide and markedly decreased MPO activity, MDA level and TNF-α content (P<0.0.05). Macroscopic and microscopic scores and biochemical markers were significantly decreased in Cromakalim-treated animals. No significant difference was observed between TNBS and Glibenclamide groups. Conclusion: Lithium exerts prominent anti-inflammatory effects on TNBS-induced colitis in rats. Potassium channels contribute to these beneficial properties.

Original languageEnglish (US)
Pages (from-to)1174-1181
Number of pages8
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume26
Issue number7
DOIs
StatePublished - Jul 2011
Externally publishedYes

Keywords

  • 2, 4, 6-trinitrobenzene sulfonic acid
  • Inflammatory bowel disease
  • Lithium
  • Potassium channel

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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