Pathophysiology of NSAID-Associated Intestinal Lesions in the Rat: Luminal Bacteria and Mucosal Inflammation as Targets for Prevention
| Autor: | Elena Piccoli, Gianfranco Natale, Matteo Fornai, Emilia Ghelardi, Cecilia Renzulli, Carmelo Scarpignato, Carolina Pellegrini, Corrado Blandizzi, Federica Fulceri, Laura Benvenuti, Daniela Gentile, Luca Antonioli, Gloria Lopez-Castejon, Erika Tirotta, Pablo Palazón-Riquelme, Rocchina Colucci |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Lydia Becker Institute Inflammation enteroprotection Pharmacology Intestinal damage Enteroprotection Intestinal bleeding Microbiota Non-steroidal anti-inflammatory drugs Rifaximin Pharmacology (medical) intestinal bleeding 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Diclofenac ResearchInstitutes_Networks_Beacons/lydia_becker_institute_of_immunology_and_inflammation medicine microbiota non-steroidal anti-inflammatory drugs Enteropathy Original Research business.industry lcsh:RM1-950 Inflammasome medicine.disease Small intestine Pathophysiology intestinal damage rifaximin lcsh:Therapeutics. Pharmacology 030104 developmental biology medicine.anatomical_structure chemistry 030211 gastroenterology & hepatology Tumor necrosis factor alpha medicine.symptom business medicine.drug |
| Zdroj: | Frontiers in Pharmacology Colucci, R, Pellegrini, C, Fornai, M, Tirotta, E, Antonioli, L, Renzulli, C, Ghelardi, E, Piccoli, E, Gentile, D, Benvenuti, L, Natale, G, Fulceri, F, Palazón-Riquelme, P, López-Castejón, G, Blandizzi, C & Scarpignato, C 2018, ' Pathophysiology of NSAID-associated intestinal lesions in the rat : Luminal bacteria and mucosal inflammation as targets for prevention ', Frontiers in Pharmacology, vol. 9, no. NOV, 01340 . https://doi.org/10.3389/fphar.2018.01340 Frontiers in Pharmacology, Vol 9 (2018) |
| ISSN: | 1663-9812 |
| Popis: | Non-steroidal anti-inflammatory drugs (NSAIDs) can damage the small intestine, mainly through an involvement of enteric bacteria. This study examined the pathophysiology of NSAID-associated intestinal lesions in a rat model of diclofenac-enteropathy and evaluated the effect of rifaximin on small bowel damage. Enteropathy was induced in 40-week old male rats by intragastric diclofenac (4 mg/kg BID, 14 days). Rifaximin (delayed release formulation) was administered (50 mg/kg BID) 1 h before the NSAID. At the end of treatments, parameters dealing with ileal damage, inflammation, barrier integrity, microbiota composition, and TLR-NF-κB-inflammasome pathway were evaluated. In addition, the modulating effect of rifaximin on NLRP3 inflammasome was tested in an in vitro cell system. Diclofenac induced intestinal damage and inflammation, triggering an increase in tissue concentrations of tumor necrosis factor and interleukin-1β, higher expression of TLR-2 and TLR-4, MyD88, NF-κB and activation of caspase-1. In addition, the NSAID decreased ileal occludin expression and provoked a shift of bacterial phyla toward an increase in Proteobacteria and Bacteroidetes abundance. All these changes were counterbalanced by rifaximin co-administration. This drug was also capable of increasing the proportion of Lactobacilli, a genus depleted by the NSAID. In LPS-primed THP-1 cells stimulated by nigericin (a model to study the NLRP3 inflammasome), rifaximin reduced IL-1β production in a concentration-dependent fashion, this effect being associated with inhibition of the up-stream caspase-1 activation. In conclusion, diclofenac induced ileal mucosal lesions, driving inflammatory pathways and microbiota changes. In conclusion, rifaximin prevents diclofenac-induced enteropathy through both anti-bacterial and anti-inflammatory activities. |
| Databáze: | OpenAIRE |
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