Digestive Diseases and Sciences

, Volume 51, Issue 9, pp 1549–1556 | Cite as

Confirmation and Prevention of Intestinal Barrier Dysfunction and Bacterial Translocation Caused by Methotrexate

Original Paper


When intestinal barrier function is damaged bacterial translocation (BT) can occur. The injury to intestinal barrier function caused by chemotherapy has been investigated in some studies, however, definitive evidence of BT caused by chemotherapy is lacking. The aim of this study was to investigate small intestinal barrier dysfunction and BT and to evaluate the preventive effect of granulocyte colony-stimulating factor (G-CSF) on intestinal barrier dysfunction and BT in a rat model of chemotherapy. Sprague-Dawley rats were treated with methotrexate (MTX; 3.5 mg/kg) for 3 days to induce intestinal barrier dysfunction and BT, gavaged Escherichia coli TG1 labeled with green fluorescent protein for 2 days to track BT, and G-CSF (10 μg/kg) for 4 days to prevent intestinal barrier dysfunction and BT. Intestinal permeability was measured by the urinary excretion rate of lactulose and mannitol following administration by gavage. Representative tissue specimens from the mesenteric lymph nodes, spleen, liver, and kidney were aseptically harvested for bacteria culture in ampicillin-supplemented medium. Light microscopy was performed on intestinal samples. MTX induced significant mucosal and villous atrophy in ileum and significantly increased intestinal permeability. MTX also induced noticeable BT. G-CSF significantly increased the mucosal thickness and villous height of the ileum and decreased intestinal permeability and BT. In conclusion, MTX caused intestinal barrier dysfunction and BT, and G-CSF prevented intestinal barrier dysfunction and BT.


Chemotherapy Methotrexate Intestinal barrier dysfunction Bacterial translocation Granulocyte colony-stimulating factor 


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Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Desheng Song
    • 1
    • 2
  • Bin Shi
    • 1
  • Hua Xue
    • 1
  • Yousheng Li
    • 1
    • 2
  • Xiaodong Yang
    • 1
  • Baojun Yu
    • 1
  • Zhe Xu
    • 1
  • Fukun Liu
    • 1
  • Jieshou Li
    • 1
  1. 1.State Key Laboratory of Research Institute of General SurgeryJinling HospitalNanjingP.R. China
  2. 2.Research Institute of General SurgeryJinling HospitalNanjingP.R. China

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