ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2010
Effect of indomethacin on bile acid-phospholipid interactions: implication for small intestinal injury induced by nonsteroidal anti-inflammatory drugs.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
35 citing papers in PubMed, 64 citations in OpenAlex.
- The proteomic differences and expression of fatty acid-binding protein 6 (FABP6) associated with gastrointestinal injury in horses with oral administration of a clinical dose of phenylbutazone.Equine veterinary journal · 2026Article
- 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
- Discovery of Focal Adhesion Kinase (FAK) activators to promote intestinal mucosal healing.European journal of medicinal chemistry · 2026Article
- Effects of Canine-Obtained Lactic-Acid Bacteria on the Fecal Microbiota and Inflammatory Markers in Dogs Receiving Non-Steroidal Anti-Inflammatory Treatment.Animals : an open access journal from MDPI · 2022Article
- Gut homeostasis, injury, and healing: New therapeutic targets.World journal of gastroenterology · 2022Review
- NSAID-Associated Small Intestinal Injury: An Overview From Animal Model Development to Pathogenesis, Treatment, and Prevention.Frontiers in pharmacology · 2022Review
- Novel Applications of NSAIDs: Insight and Future Perspectives in Cardiovascular, Neurodegenerative, Diabetes and Cancer Disease Therapy.International journal of molecular sciences · 2021Review
- Article
- Plasma membrane integrity: implications for health and disease.BMC biology · 2021Review
- The Nonsteroidal Anti-Inflammatory Drug Ketorolac Alters the Small Intestinal Microbiota and Bile Acids Without Inducing Intestinal Damage or Delaying Peristalsis in the Rat.Frontiers in pharmacology · 2021Article
- Current knowledge on non-steroidal anti-inflammatory drug-induced small-bowel damage: a comprehensive review.Journal of gastroenterology · 2020Review
- Synthesis,Acta pharmaceutica Sinica. B · 2020Article
- NSAID-Gut Microbiota Interactions.Frontiers in pharmacology · 2020Review
- Article
- Role of non-steroidal anti-inflammatory drugs on intestinal permeability and nonalcoholic fatty liver disease.World journal of gastroenterology · 2017Review
- Gata4 is critical to maintain gut barrier function and mucosal integrity following epithelial injury.Scientific reports · 2016Article
- Indomethacin injury to the rat small intestine is dependent upon biliary secretion and is associated with overgrowth of enterococci.Physiological reports · 2016Article
- Formula Feeding Predisposes Gut to NSAID-Induced Small Intestinal Injury.Clinical & experimental pharmacology · 2016Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The injurious effect of nonsteroidal anti-inflammatory drugs (NSAIDs) in the small intestine was not appreciated until the widespread use of capsule endoscopy. Animal studies found that NSAID-induced small intestinal injury depends on the ability of these drugs to be secreted into the bile. Because the individual toxicity of amphiphilic bile acids and NSAIDs directly correlates with their interactions with phospholipid membranes, we propose that the presence of both NSAIDs and bile acids alters their individual physicochemical properties and enhances the disruptive effect on cell membranes and overall cytotoxicity. We utilized in vitro gastric AGS and intestinal IEC-6 cells and found that combinations of bile acid, deoxycholic acid (DC), taurodeoxycholic acid, glycodeoxycholic acid, and the NSAID indomethacin (Indo) significantly increased cell plasma membrane permeability and became more cytotoxic than these agents alone. We confirmed this finding by measuring liposome permeability and intramembrane packing in synthetic model membranes exposed to DC, Indo, or combinations of both agents. By measuring physicochemical parameters, such as fluorescence resonance energy transfer and membrane surface charge, we found that Indo associated with phosphatidylcholine and promoted the molecular aggregation of DC and potential formation of larger and isolated bile acid complexes within either biomembranes or bile acid-lipid mixed micelles, which leads to membrane disruption. In this study, we demonstrated increased cytotoxicity of combinations of bile acid and NSAID and provided a molecular mechanism for the observed toxicity. This mechanism potentially contributes to the NSAID-induced injury in the small bowel.
Indexed as
Identifiers
What OpenQuestion holds
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.