Modulation of methotrexate-induced intestinal mucosal injury by dietary factors
Modulation of methotrexate-induced intestinal mucosal injury by dietary factors
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DOI：
10.1177/0960327119896605
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发表时间：
2019-12-26
影响因子：
2.8
通讯作者：
Furukawa, H.
中科院分区：
文献类型：
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作者：
Higuchi, T.;Yoshimura, M.;Furukawa, H.
甲氨蝶呤(MTX)引起的动物肠道粘膜损伤已被研究，以了解MTX如何引起胃肠功能紊乱，但胃肠功能紊乱的发病机制仍不确定。我们试图揭示饮食因素是如何影响MTX的肠道毒性的。小鼠在口服MTX之前，先喂普通饲料(NC)或高脂高糖饮食(HFHSD)。甲氨蝶呤显著降低高脂饲料喂养小鼠的存活率，但对小鼠肠上皮细胞有损伤作用。给予HFHSD的小鼠粪便中MTX排泄量减少。NC和HFHSD之间的饮食变化影响小鼠的存活率。饲喂高蔗糖饲料或对照饲料的小鼠的存活率高于饲喂HFHSD的小鼠。观察到喂食高脂肪高蔗糖饮食(HFHSD-M)的小鼠存活率更高，其中酪蛋白被大豆提取的蛋白取代。万古霉素组小鼠的存活率低于新霉素组。粪便微生物组和代谢组学分析表明，喂食NC和HFHSD-M的小鼠的肠道环境相似。HFHSD可能会由于肠道环境的改变而改变MTX的分布，从而改变MTX在肠上皮细胞中的毒性。
Methotrexate (MTX)-induced intestinal mucosal injury in animals has been studied to understand how MTX can cause gastrointestinal disorders, but the pathogenesis of gastrointestinal disorders is still uncertain. We have attempted to reveal how dietary factors influence intestinal toxicity due to MTX. Mice were fed normal chow (NC) or a high-fat high-sucrose diet (HFHSD) before oral administration of MTX. While MTX significantly decreased the survival rates of mice fed HFHSD, the intestinal epithelial injury was detected. MTX excretion in the feces of mice fed HFHSD was reduced. Change of diets between NC and HFHSD influences the survival. The survival rates of the mice fed a high-sucrose diet or control diet were higher than those fed HFHSD. Higher survival rates were observed in mice fed a high-fat high-sucrose diet modified (HFHSD-M) in which casein was replaced by soybean-derived proteins. The survival rates of mice treated with vancomycin were lower than those administered neomycin. Microbiome and metabolome analyses on feces suggest a similarity of the intestinal environments of mice fed NC and HFHSD-M. HFHSD may modify MTX-induced toxicity in intestinal epithelia on account of an altered MTX distribution as a result of change in the intestinal environment.