ArticleLiver international : official journal of the International Association for the Study of the Liver2015
The role of intestinal microbiota in murine models of acetaminophen-induced hepatotoxicity.
Article in Liver international : official journal of the International Association for the Study of the Liver, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Current and future directions in the treatment and prevention of drug-induced liver injury: a systematic review.Expert review of gastroenterology & hepatology · 2016Pooled it
- The Discovery of Gut Microbial Metabolites as Modulators of Host Susceptibility to Acetaminophen-Induced Hepatotoxicity.Drug metabolism and disposition: the biological fate of chemicals · 2024Review
- Role of Gut Microecology in the Pathogenesis of Drug-Induced Liver Injury and Emerging Therapeutic Strategies.Molecules (Basel, Switzerland) · 2024Review
- Toxicity of targeted anticancer treatments on the liver in myeloproliferative neoplasms.World journal of hepatology · 2023Review
- Oxidative stress mediates end-organ damage in a novel model of acetaminophen-toxicity in Drosophila.Scientific reports · 2022Article
- Probiotics: Evolving as a Potential Therapeutic Option against Acetaminophen-Induced Hepatotoxicity.Biomedicines · 2022Review
- Microbial metabolites indole derivatives sensitize mice to D-GalN/LPS induced-acute liver failureFrontiers in microbiology · 2022Article
- Oridonin Alters Hepatic Urea Cycle via Gut Microbiota and Protects against Acetaminophen-Induced Liver Injury.Oxidative medicine and cellular longevity · 2021Article
- Intestinal Dysbiosis Amplifies Acetaminophen-Induced Acute Liver Injury.Cellular and molecular gastroenterology and hepatology · 2021Article
- Contribution of the Intestinal Microbiome and Gut Barrier to Hepatic Disorders.Gastroenterology · 2020Review
- Gut Microbiota in Liver Disease: What Do We Know and What Do We Not Know?Physiology (Bethesda, Md.) · 2020Review
- Intestinal Epithelial Chemokine (C-C Motif) Ligand 7 Overexpression Enhances Acetaminophen-Induced Hepatotoxicity in Mice.The American journal of pathology · 2020Article
- Mechanisms of gastrointestinal microflora on drug metabolism in clinical practice.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2019Review
- Acetaminophen Intoxication Rapidly Induces Apoptosis of Intestinal Crypt Stem Cells and Enhances Intestinal Permeability.Hepatology communications · 2019Article
- Predicting and Understanding the Human Microbiome's Impact on Pharmacology.Trends in pharmacological sciences · 2019Review
- Gut microbiota in liver disease: too much is harmful, nothing at all is not helpful either.American journal of physiology. Gastrointestinal and liver physiology · 2019Review
- L-Fucose ameliorates high-fat diet-induced obesity and hepatic steatosis in mice.Journal of translational medicine · 2018Article
- Gut microbiota mediates diurnal variation of acetaminophen induced acute liver injury in mice.Journal of hepatology · 2018Article
- Bifidobacterium pseudocatenulatum LI09 and Bifidobacterium catenulatum LI10 attenuate D-galactosamine-induced liver injury by modifying the gut microbiota.Scientific reports · 2017Article
- Drug-induced liver injury: Do we know everything?World journal of hepatology · 2017Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsVariations in intestinal microbiota may influence acetaminophen metabolism. This study aimed to determine whether intestinal microbiota are a source of differential susceptibility to acetaminophen-induced hepatotoxicity.
methodsConventionally housed C3H/HeH (CH) and C3H/HeH germ-free (GF) mice were administered a 200 mg/kg IP dose of acetaminophen. The severity of hepatotoxicity at 8 h was assessed by histology and biochemical indices. A urinary metabolic profile was obtained using (1) H-NMR. Baseline hepatic glutathione content and CYP2E1 expression were quantified. An additional group of C3H/HeJ (LPS-r) mice were assessed to determine the contribution of LPS/TLR4 signalling.
resultsBaseline glutathione levels were significantly reduced (P = 0.03) in GF mice. CYP2E1 mRNA expression and protein levels were not altered. Interindividual variability did not differ between GF and CH groups. No significant differences in the extent of hepatocellular injury (ALT or percentage necrosis) were demonstrated. However, a milder acute liver failure (ALF) phenotype was shown in GF compared with CH mice, with reduced plasma bilirubin and creatinine and increased blood glucose. Differential acetaminophen metabolism was demonstrated. GF mice displayed a higher urinary acetaminophen-sulphate:glucuronide ratio compared with CH (P = 0.01). Urinary analysis showed metabolic differentiation of GF and CH groups at baseline and 8 h (cross-validated anova P = 1 × 10(-22) ). Interruption of TLR4 signalling in LPS-r mice had additional protective effects.
conclusionVariations in intestinal microbiota do not fully explain differential susceptibility to acetaminophen-induced hepatotoxicity. GF mice experienced some protection from secondary complications following acetaminophen overdose and this may be mediated through reduced TLR4/LPS signalling.
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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.