TY - JOUR
T1 - Chronic lithium administration ameliorates 2,4,6-trinitrobenzene sulfonic acid-induced colitis in rats; potential role for adenosine triphosphate sensitive potassium channels
AU - Daneshmand, Ali
AU - Mohammadi, Hamed
AU - Rahimian, Reza
AU - Habibollahi, Peiman
AU - Fakhfouri, Gohar
AU - Talab, Saman Shafat
AU - Mehr, Shahram Ejtemaei
AU - Dehpour, Ahmad Reza
PY - 2011/7
Y1 - 2011/7
N2 - 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.
AB - 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.
KW - 2, 4, 6-trinitrobenzene sulfonic acid
KW - Inflammatory bowel disease
KW - Lithium
KW - Potassium channel
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U2 - 10.1111/j.1440-1746.2011.06719.x
DO - 10.1111/j.1440-1746.2011.06719.x
M3 - Article
C2 - 21401719
AN - SCOPUS:79958783190
SN - 0815-9319
VL - 26
SP - 1174
EP - 1181
JO - Journal of Gastroenterology and Hepatology (Australia)
JF - Journal of Gastroenterology and Hepatology (Australia)
IS - 7
ER -