Rifaximin modulates 5-fluorouracil-induced gastrointestinal mucositis in rats.

Objective: This study assessed the protective potential of rifaximin in 5-fluorouracil (5-FU) induced intestinal mucositis in the Wistar rats'.

Materials And Methods: Twenty-nine Wistar rats were divided into 4 interventional groups of 6 animals (A, B, C and F) and one control group (M) of 5 animals. Groups A, B and C received for three days consecutively rifaximin orally: 50 mg/kg (group A), 100 mg/kg (group B) and 200 mg/kg (group C). In the fourth day, 500 mg/kg of 5-FU was administered intraperitoneally to the groups A, B, C and F. A semi-quantitative histological assessment for duodenum, jejunum and colon were obtained by rating 11 histological characteristics of mucositis from 0 (normal) to 3 (severe). Semi-quantitative grades were a measure for TLR4 immunopositive cells. Statistical comparisons used - U Test, with a Bonferroni correction for alpha (p ≤ 0.016).

Results: In the group F the most affected areas were the jejunum (median histological score 25) and the duodenum (median histological score 22). The assessment of duodenum histological lesions depicted significant difference between F and B groups (U = 1.5, p = 0.007) and between F and C groups (U = 0, p = 0.003). Graded microscopic degenerative lesions on jejunum were significantly different between F and C groups (U = 0, p = 0.004). Graded TLR4 immunopositive cells in the jejunum surface epithelium was significantly different between groups F and C (U = 2.5, p = 0.006). In the colonic mucosa, significantly differences were noted on microscopic degenerative lesions between F and A groups (U = 0, p = 0.004) and between F and C groups (U = 0, p = 0.004).

Conclusions: Pretreatment with 200 mg/kg of rifaximin for 3 consecutive days proved efficient in preventing intestinal mucosal degenerative lesions induced by 5-FU.