ArticleAlcoholism, clinical and experimental research2009
Nitric oxide-mediated intestinal injury is required for alcohol-induced gut leakiness and liver damage.
Article in Alcoholism, clinical and experimental research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 114 citations in OpenAlex.
- Ethanol, acetaldehyde, lipopolysaccharide, and neutrophil extracellular traps: four-pronged attack on gut epithelial barrier in alcohol use disorder.Anatomical record (Hoboken, N.J. : 2007) · 2026Review
- Ezetimibe Normalizes Dietary Cholesterol-Induced Exacerbation of Liver Injury in Alcohol-Fed Mice.Biomolecules · 2026Article
- Her9 is required for the migration, differentiation, and survival of neural crest cells.bioRxiv : the preprint server for biology · 2025Article
- Review
- Oral supplementation of choline attenuates the development of alcohol-related liver disease (ALD).Molecular medicine (Cambridge, Mass.) · 2024Article
- Different ethanol exposure durations affect cytochrome P450 2E1-mediated sevoflurane metabolism in rat liver.BMC anesthesiology · 2024Article
- The Interplay between Endogenous and Foodborne Pro-Oxidants and Antioxidants in Shaping Redox Homeostasis.International journal of molecular sciences · 2024Review
- Article
- Therapeutic interventions of acute and chronic liver disorders: A comprehensive review.World journal of hepatology · 2023Review
- Crosstalk between Oxidative Stress and Inflammatory Liver Injury in the Pathogenesis of Alcoholic Liver Disease.International journal of molecular sciences · 2022Review
- Gut microbiota-modulating agents in alcoholic liver disease: Links between host metabolism and gut microbiota.Frontiers in medicine · 2022Review
- Effects of a Peripherally Restricted Hybrid Inhibitor of CB1 Receptors and iNOS on Alcohol Drinking Behavior and Alcohol-Induced Endotoxemia.Molecules (Basel, Switzerland) · 2021Article
- CYP2E1 in Alcoholic and Non-Alcoholic Liver Injury. Roles of ROS, Reactive Intermediates and Lipid Overload.International journal of molecular sciences · 2021Review
- Translational Approaches with Antioxidant Phytochemicals against Alcohol-Mediated Oxidative Stress, Gut Dysbiosis, Intestinal Barrier Dysfunction, and Fatty Liver Disease.Antioxidants (Basel, Switzerland) · 2021Review
- The therapeutic potential of second and third generation CBPharmacology & therapeutics · 2020Review
- Changes in brain kynurenine levelsFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- C/EBPδ protects from radiation-induced intestinal injury and sepsis by suppression of inflammatory and nitrosative stress.Scientific reports · 2019Article
- Alcohol binge disrupts the rat intestinal barrier: the partial protective role of oleoylethanolamide.British journal of pharmacology · 2018Article
- Review
- Short-Term Intake of a Fructose-, Fat- and Cholesterol-Rich Diet Causes Hepatic Steatosis in Mice: Effect of Antibiotic Treatment.Nutrients · 2017Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
backgroundAlcoholic liver disease (ALD) requires endotoxemia and is commonly associated with intestinal barrier leakiness. Using monolayers of intestinal epithelial cells as an in vitro barrier model, we showed that ethanol-induced intestinal barrier disruption is mediated by inducible nitric oxide synthase (iNOS) upregulation, nitric oxide (NO) overproduction, and oxidation/nitration of cytoskeletal proteins. We hypothesized that iNOS inhibitors [NG-nitro-l-arginine methyl ester (l-NAME), l-N(6)-(1-iminoethyl)-lysine (l-NIL)] in vivo will inhibit the above cascade and liver injury in an animal model of alcoholic steatohepatitis (ASH).
methodsMale Sprague-Dawley rats were gavaged daily with alcohol (6 g/kg/d) or dextrose for 10 weeks +/- l-NAME, l-NIL, or vehicle. Systemic and intestinal NO levels were measured by nitrites and nitrates in urine and tissue samples, oxidative damage to the intestinal mucosa by protein carbonyl and nitrotyrosine, intestinal permeability by urinary sugar tests, and liver injury by histological inflammation scores, liver fat, and myeloperoxidase activity.
resultsAlcohol caused tissue oxidation, gut leakiness, endotoxemia, and ASH. l-NIL and l-NAME, but not the d-enantiomers, attenuated all steps in the alcohol-induced cascade including NO overproduction, oxidative tissue damage, gut leakiness, endotoxemia, hepatic inflammation, and liver injury.
conclusionsThe mechanism we reported for alcohol-induced intestinal barrier disruption in vitro - NO overproduction, oxidative tissue damage, leaky gut, endotoxemia, and liver injury - appears to be relevant in vivo in an animal model of alcohol-induced liver injury. That iNOS inhibitors attenuated all steps of this cascade suggests that prevention of this cascade in alcoholics will protect the liver against the injurious effects of chronic alcohol and that iNOS may be a useful target for prevention of ALD.
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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.