ArticleXenobiotica; the fate of foreign compounds in biological systems2014
Bacterial β-glucuronidase inhibition protects mice against enteropathy induced by indomethacin, ketoprofen or diclofenac: mode of action and pharmacokinetics.
Article in Xenobiotica; the fate of foreign compounds in biological systems, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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Who cites it
85 citing papers in PubMed, 164 citations in OpenAlex.
- Pharmacomicrobiomics: From Host-Microbiome-Drug Interactions to Clinical Translation in Precision Medicine.Metabolites · 2026Review
- What we know about prostaglandin pathway dysfunction in chronic enteropathies: From endoscopy to molecular diagnosis.Journal of translational internal medicine · 2026Article
- Concomitant COX-1 and COX-2 suppression is not sufficient to induce enteropathy associated with chronic NSAID use.The Journal of clinical investigation · 2026Article
- Characterization of fecal deglucuronidation activity in healthy subjects and in patients treated with fecal microbiota transplantation.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Sex-dependent responses in mice to indomethacin-induced organ injury and gut microbiome-targeted alleviation.Scientific reports · 2025Article
- Emerging gut microbial glycoside hydrolase inhibitors.RSC chemical biology · 2025Review
- The dopamine receptor agonist rotigotine attenuated indomethacin-induced enteropathy in the small intestinal mucosa of mice.Molecular biology reports · 2025Article
- Deciphering the universal role of gut microbiota in pollutant transformation.The ISME journal · 2025Review
- Commercially Purchased and In-House Bred C57BL/6 Mice with Different Gut Microbiota Exhibit Distinct Indomethacin-Induced Toxicities.Gut microbes reports · 2025Article
- Impact of Species and Tissue Differences on In Vitro Glucuronidation of Diclofenac.Molecules (Basel, Switzerland) · 2024Article
- Design, synthesis, and biological evaluation of (thio)urea derivatives as potentJournal of enzyme inhibition and medicinal chemistry · 2024Article
- Integrating the gut microbiome and pharmacology.Science translational medicine · 2024Review
- Genome-scale metabolic reconstruction of 7,302 human microorganisms for personalized medicine.Nature biotechnology · 2023Article
- A New Paradigm in the Relationship between Gut Microbiota and Breast Cancer: β-glucuronidase Enzyme Identified as Potential Therapeutic Target.Pathogens (Basel, Switzerland) · 2023Review
- Human Gut Microbiota and Drug Metabolism.Microbial ecology · 2023Review
- Opioid-induced microbial dysbiosis disrupts irinotecan (CPT-11) metabolism and increases gastrointestinal toxicity in a murine model.British journal of pharmacology · 2023Article
- Targeting the human gut microbiome with small-molecule inhibitors.Nature reviews. Chemistry · 2023Review
- Diagnosis by Microbial Culture, Breath Tests and Urinary Excretion Tests, and Treatments of Small Intestinal Bacterial Overgrowth.Antibiotics (Basel, Switzerland) · 2023Review
- Exploring the role of gut microbiota in advancing personalized medicine.Frontiers in microbiology · 2023Review
- Characterizing the metabolic effects of the selective inhibition of gut microbial β-glucuronidases in mice.Scientific reports · 2022Article
25 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
1. We have previously demonstrated that a small molecule inhibitor of bacterial β-glucuronidase (Inh-1; [1-((6,8-dimethyl-2-oxo-1,2-dihydroquinolin-3-yl)-3-(4-ethoxyphenyl)-1-(2-hydroxyethyl)thiourea]) protected mice against diclofenac (DCF)-induced enteropathy. Here we report that Inh-1 was equally protective against small intestinal injury induced by other carboxylic acid-containing non-steroidal anti-inflammatory drugs (NSAIDs), indomethacin (10 mg/kg, ip) and ketoprofen (100 mg/kg, ip). 2. Inh-1 provided complete protection if given prior to DCF (60 mg/kg, ip), and partial protection if administered 3-h post-DCF, suggesting that the temporal window of mucosal protection can be extended for drugs undergoing extensive enterohepatic circulation. 3. Pharmacokinetic analysis of Inh-1 revealed an absolute bioavailability (F) of 21% and a short t1/2 of <1 h. This low F was shown to be due to hepatic first-pass metabolism, as confirmed with the pan-CYP inhibitor, 1-aminobenzotriazole. 4. Using the fluorescent probe 5 (and 6)-carboxy-2',7'-dichlorofluorescein, we demonstrated that Inh-1 did not interfere with hepatobiliary export of glucuronides in gall bladder-cannulated mice. 5. These data are compatible with the hypothesis that pharmacological inhibition of bacterial β-glucuronidase-mediated cleavage of NSAID glucuronides in the small intestinal lumen can protect against NSAID-induced enteropathy caused by locally high concentrations of NSAID aglycones.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.