title: Effects of rifaximin on indomethacin-induced intestinal damage in guinea-pigs.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Regional Institute of Gastroenterology and Hepatology, University of Medicine and Pharmacy Iuliu Hatieganu, Cluj-Napoca, Romania. ciobanulidia@yahoo.com.
authors.forename: L
authors.initials: L
authors.lastname: Ciobanu
authors.forename: M
authors.initials: M
authors.lastname: Taulescu
authors.forename: R
authors.initials: R
authors.lastname: Prundus
authors.forename: B
authors.initials: B
authors.lastname: Diaconu
authors.forename: V
authors.initials: V
authors.lastname: Andreica
authors.forename: C
authors.initials: C
authors.lastname: Catoi
authors.forename: O
authors.initials: O
authors.lastname: Pascu
authors.forename: M
authors.initials: M
authors.lastname: Tantau
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D004751:Enteritis / Q000188:drug therapy* / Q000201:enzymology / Q000382:microbiology / Q000473:pathology; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006168:Guinea Pigs; D007150:Immunohistochemistry; D007213:Indomethacin / Q000009:adverse effects*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D020556:Neutrophil Infiltration / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D012294:Rifamycins / Q000008:administration & dosage / Q000627:therapeutic use*; D000078262:Rifaximin
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005765:Gastrointestinal Agents; D012294:Rifamycins; D052247:Nitric Oxide Synthase Type II; D000078262:Rifaximin; D007213:Indomethacin