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

J Gastroenterol Hepatol. 2011 Jul;26(7):1174-81. doi: 10.1111/j.1440-1746.2011.06719.x.


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 10 mg 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.

Publication types

  • Comparative Study

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Animals
  • Colitis / chemically induced
  • Colitis / drug therapy*
  • Colitis / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Follow-Up Studies
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / pathology
  • Lithium / administration & dosage*
  • Male
  • Potassium Channels / metabolism*
  • Rats
  • Rats, Wistar
  • Time Factors
  • Trinitrobenzenesulfonic Acid / toxicity


  • Potassium Channels
  • Adenosine Triphosphate
  • Trinitrobenzenesulfonic Acid
  • Lithium