Research Article

The effects of low-dose methotrexate on endothelial dysfunction and programmed cell death (apoptosis) in 2,4,6 Trinitrobenzensulphonic acid (TNBSA) induced model of experimental colitis

  • Eray Kara
  • Aslan Sakarya
  • Ahmet Var
  • Seda Vatansever

Turk J Colorectal Dis 2010;20(2):66-75


Currently, the medical investigations on alternative drug therapies in inflammatory bowel disease (IBD) have been increased. Methotrexate (Mtx) has been used in the management of IBD due to its anti-inflammatory effects. It’s aimed to investigate the effects of Mtx on endothelial dysfunction and colonic mucosa in experimental acute colitis.


This study was carried out on 36 rats induced for colitis by 2,4,6 trinitrobenzensulfonic (TNBS) acid, and they were divided into 3 groups: Group I: TNBS+Mtx, Group II: TNBS, Group III: saline enema. While single dose of Mtx administered as an intramuscular injection in drug group (Group I), only colitis was induced in the second group (Group II). 1 ml/kg/daily of saline enema was administered intrarectally to the third group.On the seventh day of the experiment, animals were sacrificed and then distal colons were removed surgically for immunohistochemical and biochemical analyses. Colonic mucosal NO, iNOS, eNOS, MPO activity, macroscopic changes and histomorphology were evaluated.


Mtx reduced MPO activity, TNF-α, NO, iNOS and eNOS releases from inflamed colonic tissue and healed mucosal damage in experimental model of acute colitis.Additionally, Mtx suppressed apoptotic and proliferative processes in inflamed colonic tissue.


In conclusion; Mtx may be suggested as an alternate agent especially in acute attack episodes of inflammatory bowel disease.

Keywords: Methotrexate, inflammatory bowel disease, apoptosis