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益生菌可逆转慢性顺铂暴露引起的小鼠近端结肠的形态和功能改变。

Prebiotics counteract the morphological and functional changes secondary to chronic cisplatin exposition in the proximal colon of mice.

机构信息

Research Unit of Histology and Embryology, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.

Section of Physiological Sciences, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.

出版信息

J Cell Mol Med. 2024 Mar;28(6):e18161. doi: 10.1111/jcmm.18161.

Abstract

Cisplatin is an antimitotic drug able to cause acute and chronic gastrointestinal side effects. Acute side effects are attributable to mucositis while chronic ones are due to neuropathy. Cisplatin has also antibiotic properties inducing dysbiosis which enhances the inflammatory response, worsening local damage. Thus, a treatment aimed at protecting the microbiota could prevent or reduce the toxicity of chemotherapy. Furthermore, since a healthy microbiota enhances the effects of some chemotherapeutic drugs, prebiotics could also improve this drug effectiveness. We investigated whether chronic cisplatin administration determined morphological and functional alterations in mouse proximal colon and whether a diet enriched in prebiotics had protective effects. The results showed that cisplatin caused lack of weight gain, increase in kaolin intake, decrease in stool production and mucus secretion. Prebiotics prevented increases in kaolin intake, changes in stool production and mucus secretion, but had no effect on the lack of weight gain. Moreover, cisplatin determined a reduction in amplitude of spontaneous muscular contractions and of Connexin (Cx)43 expression in the interstitial cells of Cajal, changes that were partially prevented by prebiotics. In conclusion, the present study shows that daily administration of prebiotics, likely protecting the microbiota, prevents most of the colonic cisplatin-induced alterations.

摘要

顺铂是一种抗有丝分裂药物,能够引起急性和慢性胃肠道副作用。急性副作用归因于黏膜炎,而慢性副作用则是由于神经病变。顺铂还具有抗生素特性,诱导菌群失调,从而增强炎症反应,加重局部损伤。因此,旨在保护微生物群的治疗方法可以预防或减少化疗的毒性。此外,由于健康的微生物群增强了一些化疗药物的效果,因此益生元也可以提高这种药物的效果。我们研究了慢性顺铂给药是否会导致小鼠近端结肠的形态和功能改变,以及富含益生元的饮食是否具有保护作用。结果表明,顺铂导致体重增加减少、高岭土摄入量增加、粪便产生减少和黏液分泌减少。益生元可预防高岭土摄入量增加、粪便产生和黏液分泌改变,但对体重增加减少没有影响。此外,顺铂导致自发性肌肉收缩幅度和 Cajal 间质细胞中连接蛋白(Cx)43 表达减少,这些变化部分被益生元预防。总之,本研究表明,每日给予益生元可能通过保护微生物群来预防大部分结肠顺铂诱导的改变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92b2/10915824/22587d0c0084/JCMM-28-e18161-g005.jpg

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