Prokinetic effects of diatrizoate meglumine (Gastrografin®) in a zebrafish for opioid-induced constipation model

泛影葡胺(Gastrografin®)对斑马鱼阿片类药物诱发便秘模型的促动力作用

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作者:Dongwoo Kim, Soonil Koun, Seung Young Kim, Young Ran Ha, Jung Wan Choe, Sung Woo Jung, Jong Jin Hyun, Young Kul Jung, Ja Seol Koo, Hyung Joon Yim, Sang Woo Lee

Abstract

Constipation is a common disease that reduces life quality. Drugs of various mechanisms are being developed to resolve this affliction. Intestinal motility can be easily monitored in zebrafish, and so we selected this organism to develop a constipation model to measure drug-induced prokinetic effects. In this study, intestinal motility was monitored in zebrafish by tracking intestinal transit using fluorescence, after which an opioid-induced constipation model was established using loperamide. We then evaluated the prokinetic effect of diatrizoate meglumine (Gastrografin®), which has been empirically used to treat post-operative ileus or adhesive small bowel obstructions. Diatrizoate meglumine was effective in promoting bowel movements in an opioid-induced zebrafish constipation model and its prokinetic effect was associated with an increased expression of interstitial cells of Cajal (ICC) markers. Therefore, the loperamide-induced zebrafish constipation model developed herein is a promising tool to evaluate novel constipation therapies.

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