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

AIM: Enterobacterial transloca - tion into the gut mucosa is the first step re - quired for activation of neutrophils and in - ducible nitric oxide synthase (iNOS), involved in the pathogenesis of indomethacin-induced in - testinal lesions. Rifaximin may limit NSAID-as - sociated intestinal damage by decreasing the bacterial load.We aimed to study the effect of ri - faximin on indomethacin-induced intestinal damage in guinea-pigs. MATERIALS AND METHODS: Twenty-four guinea pigs, equally divided in four intervention - al groups (A-D), received indomethacin, given orally once daily (30 mg/kg) for three consecu - tive days. In groups B, C, D different doses of ri - faximin (50 mg/kg, 100 mg/kg and 200 mg/kg) were given orally two hours before in - dometachin administration. Semi-quantitative grades were measure for gross findings, degen - erative lesions, neutrophils and eosinophils in - filtrates 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, en - dothelium damage and iNOS immunopositivity found no difference between A and B groups. Sig - nificant fewer gross findings (U = 3, p = 0.015), mi - croscopic 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 de - generative 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.