The protective role of montelukast against intestinal ischemia-reperfusion injury in rats

Sci Rep. 2015 Oct 26:5:15787. doi: 10.1038/srep15787.

Abstract

Several drugs are effective in attenuating intestinal ischemia-reperfusion injury (IRI); however little is known about the effect of montelukast. Fifty rats were randomly assigned to 3 groups: model group (operation with clamping), sham group (operation without clamping), and study group (operation with clamping and 0.2, 2 and 20 mg/kg montelukast pretreatment). Intestinal ischemia-reperfusion was performed by occlusion (clamping) of the arteria mesenterica anterior for 45 min, followed by 24 h reperfusion. Intestinal IRI in the model group led to severe damage of the intestinal mucosa, liver and kidney. The Chiu scores of the intestines from the study group (2 and 20 mg/kg) were lower than that of the model group. Intestinal IRI induced a marked increase in CysLTR1, Caspase-8 and -9 expression in intestine, liver and kidney, which were markedly reduced by preconditioning with 2 mg/kg montelukast. Preconditioning with 2 g/kg montelukast significantly attenuated hepatic tissue injury and kidney damage, and decreased plasma interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels in plasma after intestinal IRI. In conclusion, preconditioning with montelukast could attenuate intestinal IRI and the subsequent systemic inflammatory response in rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / pharmacology
  • Acetates / therapeutic use*
  • Acute-Phase Proteins / metabolism
  • Alanine Transaminase / blood
  • Animals
  • Aspartate Aminotransferases / blood
  • Caspase 8 / metabolism
  • Caspase 9 / metabolism
  • Cyclopropanes
  • Interleukin-6 / blood
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / pathology
  • Lipocalin-2
  • Lipocalins / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Protective Agents / pharmacology
  • Protective Agents / therapeutic use*
  • Proto-Oncogene Proteins / metabolism
  • Quinolines / pharmacology
  • Quinolines / therapeutic use*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Receptors, Leukotriene / genetics
  • Receptors, Leukotriene / metabolism
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*
  • Sulfides
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Acetates
  • Acute-Phase Proteins
  • Cyclopropanes
  • Interleukin-6
  • Lcn2 protein, rat
  • Lipocalin-2
  • Lipocalins
  • Protective Agents
  • Proto-Oncogene Proteins
  • Quinolines
  • RNA, Messenger
  • Receptors, Leukotriene
  • Sulfides
  • Tumor Necrosis Factor-alpha
  • cysteinyl leukotriene receptor 2
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Caspase 8
  • Caspase 9
  • montelukast