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Early Disturbance of Microvascular Function Precedes Chemotherapy-Induced Intestinal Injury

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Abstract

Intestinal injury 4–48 hr after cytotoxic therapy (etoposide phosphate, 100 mg/kg body weight [bw], intravenously [i.v.]) was studied in rats using ligated intestinal loops. Chromium-51 ethylenediaminetetraacetic acid (51Cr-EDTA) and rubidium-86 chloride (86RbCl) were deposited intraluminally to determine the extent of the increase in intestinal permeability and ion channel disruption. Evans Blue (EB) was used for detection of endothelial leakage. Intestinal morphology was documented. Endothelial dysfunction, as observed by an increased extravasation of EB, was evident already 4 hr after cytotoxic therapy. Intestinal epithelial injury, as observed by an increase in 51Cr-EDTA permeation and a decrease in 86Rb absorption, occurred after 48 hr. Finally, histology disclosed a reduced crypt cell proliferation, displayed as a decrease in Ki67-positive cells. The findings suggest that, in the development of intestinal injury after cytotoxic therapy, endothelial disruption is an early event, whereafter epithelial dysfunction and crypt stem cell arrest occur. This knowledge could be of importance in the design of future intervention trials.

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Authors and Affiliations

  1. Department of Oncology, Sahlgren’s University Hospital, Göteberg, Sweden

    E. Abel MD, T. Ekman MD, PhD, E. Warnhammar MD, R. Hultborn MD, PhD & E. Jennische MD, PhD

  2. Departments of Clinical Bacteriology, University of Göteborg, Göteberg, Sweden

    S. Lange MD, PhD

Authors
  1. E. Abel MD
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  2. T. Ekman MD, PhD
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  3. E. Warnhammar MD
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  4. R. Hultborn MD, PhD
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  5. E. Jennische MD, PhD
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  6. S. Lange MD, PhD
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Correspondence to E. Abel MD.

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Abel, E., Ekman, T., Warnhammar, E. et al. Early Disturbance of Microvascular Function Precedes Chemotherapy-Induced Intestinal Injury. Dig Dis Sci 50, 1729–1733 (2005). https://doi.org/10.1007/s10620-005-2926-9

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  • DOI: https://doi.org/10.1007/s10620-005-2926-9

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