Effects of rifaximin on indomethacin-induced intestinal damage in guinea-pigs

L. Ciobanu, M. Taulescu, R. Prundus, B. Diaconu, V. Andreica, C. Catoi, O. Pascu, M. Tantau

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

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• Gastroenterology

AIM: Enterobacterial translocation into the gut mucosa is the first step required for activation of neutrophils and inducible nitric oxide synthase (iNOS), involved in the pathogenesis of indomethacin-induced intestinal lesions. Rifaximin may limit NSAID-associated intestinal damage by decreasing the bacterial load. We aimed to study the effect of rifaximin on indomethacin-induced intestinal damage in guinea-pigs.

MATERIALS AND METHODS: Twenty-four guinea pigs, equally divided in four interventional groups (A-D), received indomethacin, given orally once daily (30 mg/kg) for three consecutive days. In groups B, C, D different doses of rifaximin (50 mg/kg, 100 mg/kg and 200 mg/kg) were given orally two hours before indometachin administration. Semi-quantitative grades were measure for gross findings, degenerative lesions, neutrophils and eosinophils infiltrates and iNOS immunopositivity. Statistical comparisons used Mann Whitney Test, with a Bonferroni correction for alpha (p ≤ 0.016).

RESULTS: Statistical analysis of graded gross findings, microscopic degenerative lesions, endothelium damage and iNOS immunopositivity found no difference between A and B groups. Significant fewer gross findings (U = 3, p = 0.015), microscopic degenerative lesions (U = 2, p = 0.008) and lower grades for iNOS immunopositivity (U = 0, p = 0.002) were found in group C compared with group A. In group D, significant lower grades for iNOS immunopositivity were obtained (U = 0, p = 0.002) compared with group A and fewer degenerative lesions without reaching statistical significance (U = 4, p = 0.026).

CONCLUSIONS: 100 mg/kg of rifaximin proved efficient in preventing gut degenerative lesions induced by indomethacin in a guinea pig model, the iNOS activity being significantly decreased.

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