Effects of exogenous zinc supplementation on intestinal epithelial repair in vitro

Cario, Jung, H d'Heureuse, Schulte… - European Journal of …, 2000 - Wiley Online Library
Cario, Jung, H d'Heureuse, Schulte, Sturm, Wiedenmann, Goebell, Dignass
European Journal of Clinical Investigation, 2000Wiley Online Library
Background Substitution of zinc modulates antioxidant capabilities within the intestinal
mucosa and improves intestinal wound healing in zinc‐deficient patients with inflammatory
bowel diseases. The aim of this study was to characterize the modulating effects of zinc on
intestinal epithelial cell function in vitro. Materials and methods The effects of zinc on
intestinal epithelial cell morphology were assessed by phase contrast and transmission
electron microscopy using the non‐transformed small intestinal epithelial cell line IEC‐6 …
Background
Substitution of zinc modulates antioxidant capabilities within the intestinal mucosa and improves intestinal wound healing in zinc‐deficient patients with inflammatory bowel diseases. The aim of this study was to characterize the modulating effects of zinc on intestinal epithelial cell function in vitro.
Materials and methods
The effects of zinc on intestinal epithelial cell morphology were assessed by phase contrast and transmission electron microscopy using the non‐transformed small intestinal epithelial cell line IEC‐6. Zinc‐induced apoptosis was assessed by DNA fragmentation analysis, lactate dehydrogluase (LDH) release and flow cytometry with propidium iodine staining. Furthermore, the effects of zinc on IEC‐6 cell proliferation were assessed using a colorimetric thiazolyl blue (MTT) assay and on IEC‐6 cell restitution using an in vitro wounding model.
Results
Physiological concentrations of zinc (25 μm) did not significantly alter the morphological appearance of IEC‐6 cells. However, a 10‐fold higher dose of zinc (250 μm) induced epithelial cell rounding, loss of adherence and apoptotic characteristics. While physiological zinc concentrations (< 100 μm) did not induce apoptosis, supraphysiological zinc concentrations (> 100 μm) caused apoptosis. Physiological concentrations of zinc (6.25–50 μm) had no significant effect on intestinal epithelial cell proliferation. In contrast, physiological concentrations of zinc (12.5–50 μm) significantly enhanced epithelial cell restitution through a transforming growth factor‐β (TGFβ)‐independent mechanism. Simultaneous addition of TGFβ and zinc resulted in an additive stimulation of IEC‐6 cell restitution.
Conclusion
Zinc may promote intestinal epithelial wound healing by enhancement of epithelial cell restitution, the initial step of epithelial wound healing. Zinc supplementation may improve epithelial repair; however, excessive amounts of zinc may cause tissue injury and impair epithelial wound healing.
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