Rifaximin modulates 5-fluorouracil-induced gastrointestinal mucositis in rats

L. Ciobanu, M. Tantau, S. Valean, A. Parau, I. Bedecean, R. Mîrleneanu, C. Berce, C. Catoi, M. Taulescu

University of Medicine and Pharmacy Iuliu Hatieganu, Cluj-Napoca, Romania. ciobanulidia@yahoo.com

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• Pharmacology

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.

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