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

Abstract

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 microg/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.

Establishment of a functional secretory IgA transcytosis model system in vitro for functional food screening

“…Studies showed that infections caused by enteritis are caused primarily by the intestinal microflora through bacterial turbulence and translocation (Song et al 2006a;Song et al 2006b;Stecher and Hardt 2008). As the vulnerable intestinal mucosa is exposed to a multitude of ingested or inhaled microorganisms, environmental and food antigens, the first-line protection of the mucosal surface area depends on an active export of SIgA.…”

Glutamine prevents intestinal mucosal injury induced by cyclophosphamide in rats

“…Various clinical and experimental studies have demonstrated that intestinal mucosal injury induced by chemotherapy impairs gut barrier function and leads to bacterial translocation, resulting in the systemic inflammatory response [11,12]. Therefore, treatments that prevent intestinal mucosal injury following chemotherapy will comprise novel therapeutic strategies in maintaining gut barrier function and improving outcome in patients receiving chemotherapy.…”

Metotreksatın Neden Olduğu Gastrointestinal Kanaldan Bakteriyel Translokasyonun Önlenmesinde Hesperidinin Etkinliği

“…One recent study showed that MTX induced severe damage of small intestinal mucosa and barrier functions in rats. Granulocyte colony-stimulating factor (G-CSF) given subcutaneously to rats is significantly effective in the preventing of bacterial translocation and morphological distortion after complete mechanical intestinal obstruction [3] .…”

“… İletişim (Correspondence)  +90 322 3386637  kdagli01@gmail.com to cause morphological injuries included intestinal barrier function damage in the mucosa of small intestine its association with bacterial translocation is still unclear [3] . Reducing mucosal damage is important in order to lower the side-effects in patients receiving chemotherapy to a minimum.…”