Small bowel protection against NSAID-injury in rats: Effect of rifaximin, a poorly absorbed, GI targeted, antibiotic

Autor: Emilia Ghelardi, Matteo Fornai, Carolina Pellegrini, Marina Flaibani, Erika Tirotta, Deborah Sacco, Carmelo Scarpignato, Cecilia Renzulli, Rocchina Colucci, Corrado Blandizzi, Alessia Bartalucci, Gianfranco Natale, Luca Antonioli
Rok vydání: 2016
Předmět:
DNA
Bacterial
Male
Pathology
medicine.medical_specialty
Indomethacin
Firmicutes
Ileum
Pharmacology
Intestinal damage
Rifaximin
Intestinal absorption
Bacterial flora
Enteroprotection
Intestinal bleeding
Nonsteroidal anti-inflammatory drugs
Jejunum
03 medical and health sciences
chemistry.chemical_compound
Bacterial flora
0302 clinical medicine
Malondialdehyde
Proteobacteria
medicine
Animals
Large intestine
Enteropathy
Rats
Wistar
Peroxidase
biology
Tumor Necrosis Factor-alpha
Anti-Inflammatory Agents
Non-Steroidal
medicine.disease
Bacterial flora
Enteroprotection
Intestinal bleeding
Intestinal damage
Nonsteroidal anti-inflammatory drugs
Rifaximin
Rifamycins
Enteroprotection
Small intestine
Anti-Bacterial Agents
Intestinal Diseases
Intestinal bleeding
medicine.anatomical_structure
Intestinal Absorption
chemistry
030220 oncology & carcinogenesis
Myeloperoxidase
biology.protein
030211 gastroenterology & hepatology
Zdroj: Pharmacological Research. 104:186-196
ISSN: 1043-6618
DOI: 10.1016/j.phrs.2015.12.031
Popis: Nonsteroidal anti-inflammatory drugs, besides exerting detrimental effects on the upper digestive tract, can also damage the small and large intestine. Although the underlying mechanisms remain unclear, there is evidence that enteric bacteria play a pivotal role. The present study examined the enteroprotective effects of a delayed-release formulation of rifaximin-EIR (R-EIR, 50mg/kg BID, i.g.), a poorly absorbed antibiotic with a broad spectrum of antibacterial activity, in a rat model of enteropathy induced by indomethacin (IND, 1.5mg/kg BID for 14 days) administration. R-EIR was administered starting 7 days before or in concomitance with IND administration. At the end of treatments, blood samples were collected to evaluate hemoglobin (Hb) concentration (as an index of digestive bleeding). Small intestine was processed for: (1) histological assessment of intestinal damage (percentage length of lesions over the total length examined); (2) assay of tissue myeloperoxidase (MPO) and TNF levels, as markers of inflammation; (3) assay of tissue malondialdehyde (MDA) and protein carbonyl concentrations, as an index of lipid and protein peroxidation, respectively; (4) evaluation of the major bacterial phyla. IND significantly decreased Hb levels, this effect being significantly blunted by R-EIR. IND also induced the occurrence of lesions in the jejunum and ileum. In both intestinal regions, R-EIR significantly reduced the percentage of lesions, as compared with rats receiving IND alone. Either the markers of inflammation and tissue peroxidation were significantly increased in jejunum and ileum from IND-treated rats. However, in rats treated with R-EIR, these parameters were not significantly different from those observed in controls. R-EIR was also able to counterbalance the increase in Proteobacteria and Firmicutes abundance induced by INDO. To summarize, R-EIR treatment significantly prevents IND-induced intestinal damage, this enteroprotective effect being associated with a decrease in tissue inflammation, oxidative stress and digestive bleeding as well as reversal of NSAID-induced alterations in bacterial population.
Databáze: OpenAIRE
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