Rifaximin alleviates irinotecan-induced diarrhea in mice model

作者：Cheng-Yi Huang, Huiyin Lan, Minghua Bai, Jinggang Chen, Shengkun Xu, Quanquan Sun, Qianping Chen, Wei Mao, Jin Jiang, Ji Zhu · 发表于：Annals of Medicine · 年份：2024 · DOI：10.1080/07853890.2024.2429029 · 被引用次数：7 · 研究领域：Pneumocystis jirovecii pneumonia detection and treatment、Cancer therapeutics and mechanisms、Phenothiazines and Benzothiazines Synthesis and Activities

Background Irinotecan is a chemotherapeutic drug widely used to treat solid tumors. However, its effectiveness is limited by the severely delayed onset of diarrhea. This study aimed to confirm the protective effects of the non-systemic oral antibiotic rifaximin on irinotecan-induced mucositis in mice model.Materials and methods Six to eight week-old BALB/c mice were treated with saline, irinotecan (50 mg/kg, i.p. once daily), rifaximin (50 mg/kg, p.o. twice daily), or irinotecan + rifaximin for 9 consecutive days. Signs of diarrhea, bloody diarrhea, and body weight were monitored daily. Intestinal tissues were harvested for histopathological analysis and quantitative PCR. SN38 and SN38G concentration in intestine were detected using LC-MS analysis. Intestinal bacteria β-glucuronidase (BGUS) activity was detected using mouse feces. We performed 16S rRNA sequencing to investigate the gut microbiota composition. Gut permeability was tested in vivo by measuring the fluorescein isothiocyanate-dextran intensity in the serum.Results Rifaximin reduced the frequency of delayed diarrhea and attenuated the severity of diarrhea caused by irinotecan in mice. Rifaximin significantly inhibited SN38 exposure in intestine and irinotecan-induced increase in BGUS activity. Rifaximin alleviated intestinal mucosal inflammation, prevented intestinal epithelial damage caused by irinotecan, and maintained gut barrier function. Moreover, the consecutive use of rifaximin did not cause a disorder in gu...