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KMID : 0882420070730030258
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Korean Journal of Medicine
2007 Volume.73 No. 3 p.258 ~ p.266
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Acute gut injury and bacterial translocation in a rat model with combined oral administration of methotrexate and diclofenac
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Kim Jeong-Wook
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Abstract
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Background : NSAIDs and methotrexate induce gut damage and bacterial translocation (BT). However, there is no
study examining the combined effects of methotrexate and NSAID on gut damage and BT. We examined the combined
effects of methotrexate and NSAID-induced enteropathy and bacterial translocation in an experimental animal model.
Methods : Rats received either no drug, NSAID alone (diclofenac 80 mg/kg and 120 mg/kg per os), methorexate alone(20 mg/kg per os) or NSAID with methotrexate. Gut barrier dysfunction, the degree of intestinal adhesion, stool pellet
number, bacterial number of total aerobes and Gram negatives in the distal ileal and cecal contents and the number of
Gram negatives in the mesenteric lymph nodes, liver, spleen, kidney and heart were measured.
Results : Administration of diclofenac or methotrexate alone caused an increase in gut barrier dysfunction and
intestinal adhesion and a decrease in stool pellet number. Administration of diclonfenac alone induced enteric bacterial
overgrowth and increased BT to the mesenteric lymph nodes, liver, spleen, kidney and heart. Administration of
methotrexate alone induced enteric bacterial undergrowth and BT to the mesenteric lymph nodes, liver, spleen but not
to the kidney and heart. The supplements with methotrexate increased the NSAID-induced gut barrier dysfunction and
intestinal adhesion, and decreased the stool pellet number. However, the reduced NSAID-induced enteric Gram negative
bacterial overgrowth (with a dose of diclofenac of 80 mg/kg) and BT to the liver, spleen, kidney and heart.
Conclusion : Methotrexate increases NSAID-induced intestinal damage, but reduces NSAID-induced BT to the liver, spleen, kidney and heart in experimental animals.(Korean J Med 73:258-266, 2007)
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KEYWORD
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Anti-inflammatory agents, Non-steroidal, Methotrexate, Bacterial translocation, Adverse effects
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