Rifaximin modulates 5-fluorouracil-induced gastrointestinal mucositis in rats

Area of Science:

• Gastroenterology
• Pharmacology
• Oncology

Background:

• Chemotherapy, particularly 5-fluorouracil (5-FU), commonly causes gastrointestinal toxicity, including mucositis.
• Intestinal mucositis significantly impacts patient quality of life and treatment adherence.
• Rifaximin, a non-absorbable antibiotic, has shown anti-inflammatory properties that may mitigate chemotherapy-induced damage.

Purpose of the Study:

• To evaluate the protective effects of rifaximin against 5-fluorouracil (5-FU)-induced intestinal mucositis in a Wistar rat model.
• To determine the optimal dosage of rifaximin for preventing 5-FU-induced intestinal damage.

Main Methods:

• Wistar rats were divided into groups receiving varying doses of rifaximin (50, 100, 200 mg/kg) or a control, followed by intraperitoneal administration of 5-FU.
• Histological assessments of the duodenum, jejunum, and colon were performed to evaluate mucositis severity.
• TLR4 immunopositive cells were quantified as a marker of inflammation.

Main Results:

• 5-fluorouracil (5-FU) induced significant histological damage in the jejunum and duodenum.
• Pretreatment with 200 mg/kg of rifaximin demonstrated a significant reduction in duodenal and jejunal lesions compared to the control group.
• Rifaximin at 200 mg/kg also significantly reduced TLR4 expression in the jejunum and degenerative lesions in the colon.

Conclusions:

• Pretreatment with 200 mg/kg of rifaximin effectively prevented 5-fluorouracil-induced intestinal mucosal degenerative lesions in Wistar rats.
• Rifaximin shows promise as a therapeutic agent to mitigate chemotherapy-induced gastrointestinal toxicity.