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Important Endpoints and Proliferative Markers to Assess Small Intestinal Injury and Adaptation using a Mouse Model of Chemotherapy-Induced Mucositis
Published on: May 12, 2019
Betulin Alleviates 5-Fluorouracil-Induced Intestinal Mucositis in Mice
Shiyi Sun1, Ziming Wang1, Haoyue Xu1
1National and Local Joint Engineering Research Center of Ecological Treatment Technology for Urban Water Pollution, Zhejiang Provincial Key Laboratory for Water Environment and Marine Biological Resources Protection, College of Life and Environmental Science, Wenzhou University, Wenzhou 325035, China.
Betulin (BE) shows therapeutic potential for chemotherapy-induced intestinal mucositis (CIM) caused by 5-fluorouracil (5-FU). BE treatment improved gut health, reduced inflammation, and modulated gut microbiota in a mouse model.
Area of Science:
- Pharmacology
- Gastroenterology
- Microbiology
Background:
- Chemotherapy-induced intestinal mucositis (CIM) is a severe side effect of cancer treatment, frequently linked to 5-fluorouracil (5-FU).
- Betulin (BE), a pentacyclic triterpenoid, possesses known anti-inflammatory and cytoprotective properties.
- The therapeutic efficacy of BE in managing 5-FU-induced CIM has not been previously investigated.
Purpose of the Study:
- To evaluate the therapeutic effects of Betulin (BE) in a murine model of 5-fluorouracil (5-FU)-induced intestinal mucositis (CIM).
- To investigate the impact of BE on histopathological changes, apoptosis, inflammation, and gut microbiota composition in 5-FU-treated mice.
Main Methods:
- BALB/c mice were administered 5-FU to induce CIM, followed by oral administration of varying doses of BE.
- Evaluated clinical signs, colon morphometry, histopathology, apoptosis markers (Bax, Bcl-2, caspase-3), inflammatory markers (Tnf, Nos2), and gut microbiota.
- Specific focus on the 200 mg/kg BE dose for detailed molecular and microbial analysis.
Main Results:
- BE treatment significantly improved clinical outcomes, including body weight, diarrhea, and food intake, alongside enhanced colon morphology and reduced histological damage.
- At 200 mg/kg, BE notably decreased pro-inflammatory markers (Tnf, Nos2, iNOS) and apoptosis indicators (Bax, caspase-3), while increasing anti-apoptotic protein (Bcl-2).
- Exploratory analysis of gut microbiota in the 200 mg/kg group revealed alterations in microbial diversity and community structure.
Conclusions:
- Betulin (BE) demonstrates significant therapeutic potential for mitigating 5-fluorouracil (5-FU)-induced intestinal mucositis (CIM).
- The observed benefits are associated with the modulation of apoptotic pathways, reduction in inflammation, and alterations in gut microbiota composition.
- Further research is warranted to elucidate the precise mechanisms underlying BE's efficacy in CIM.
