ArticleToxicological sciences : an official journal of the Society of Toxicology2014
Increased susceptibility to methotrexate-induced toxicity in nonalcoholic steatohepatitis.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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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
33 citing papers in PubMed, 61 citations in OpenAlex.
- Nonalcoholic steatohepatitis increases plasma retention of sorafenib-glucuronide in a mouse model by altering hepatocyte hopping.Acta pharmaceutica Sinica. B · 2024Article
- Representative Rodent Models for Renal Transporter Alterations in Human Nonalcoholic Steatohepatitis.Drug metabolism and disposition: the biological fate of chemicals · 2023Article
- Renal Transporter Alterations in Patients with Chronic Liver Diseases: Nonalcoholic Steatohepatitis, Alcohol-Associated, Viral Hepatitis, and Alcohol-Viral Combination.Drug metabolism and disposition: the biological fate of chemicals · 2023Article
- Predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in non-alcoholic steatohepatitis patients.Acta pharmaceutica Sinica. B · 2023Review
- Preparation of Polyvinyl Imine Modified Carbon Quantum Dots and Their Application in Methotrexate Detection.Molecules (Basel, Switzerland) · 2022Article
- Effects of asparaginases and L-carnitine on Western-diet-induced hepatosteatosis in mice.F1000Research · 2022Article
- A Two-Way Interaction between Methotrexate and the Gut Microbiota of Male Sprague-Dawley Rats.Journal of proteome research · 2020Article
- Modulation of Tetrachloroethylene-Associated Kidney Effects by Nonalcoholic Fatty Liver or Steatohepatitis in Male C57BL/6J Mice.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Gene-by-Environment Interaction of BcrpDrug metabolism and disposition: the biological fate of chemicals · 2018Article
- Alcohol Metabolism in the Progression of Human Nonalcoholic Steatohepatitis.Toxicological sciences : an official journal of the Society of Toxicology · 2018Article
- Misregulation of membrane trafficking processes in human nonalcoholic steatohepatitis.Journal of biochemical and molecular toxicology · 2018Article
- Asking the Right Questions With Animal Models: Methionine- and Choline-Deficient Model in Predicting Adverse Drug Reactions in Human NASH.Toxicological sciences : an official journal of the Society of Toxicology · 2018Article
- Transporter-Mediated Alterations in Patients With NASH Increase Systemic and Hepatic Exposure to an OATP and MRP2 Substrate.Clinical pharmacology and therapeutics · 2017Article
- Pediatric Cytochrome P450 Activity Alterations in Nonalcoholic Steatohepatitis.Drug metabolism and disposition: the biological fate of chemicals · 2017Article
- Digestive system in psoriasis: an update.Archives of dermatological research · 2017Review
- Nonalcoholic Fatty Liver Disease Is a Susceptibility Factor for Perchloroethylene-Induced Liver Effects in Mice.Toxicological sciences : an official journal of the Society of Toxicology · 2017Article
- Effect of Liver Disease on Hepatic Transporter Expression and Function.Journal of pharmaceutical sciences · 2017Review
- Impaired N-linked glycosylation of uptake and efflux transporters in human non-alcoholic fatty liver disease.Liver international : official journal of the International Association for the Study of the Liver · 2017Article
- Impact of Nonalcoholic Fatty Liver Disease on Toxicokinetics of Tetrachloroethylene in Mice.The Journal of pharmacology and experimental therapeutics · 2017Article
- Role of nonalcoholic fatty liver disease as risk factor for drug-induced hepatotoxicity.Journal of clinical and translational research · 2017Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Hepatic drug metabolizing enzymes and transporters play a crucial role in determining the fate of drugs, and alterations in liver function can place individuals at greater risk for adverse drug reactions (ADRs). We have shown that nonalcoholic steatohepatitis (NASH) leads to changes in the expression and localization of enzymes and transporters responsible for the disposition of numerous drugs. The purpose of this study was to determine the effect of NASH on methotrexate (MTX) disposition and the resulting toxicity profile. Sprague Dawley rats were fed either a control or methionine-choline-deficient diet for 8 weeks to induce NASH, then administered a single ip vehicle, 10, 40, or 100 mg/kg MTX injection followed by blood, urine, and feces collection over 96 h with terminal tissue collection. At the onset of dosing, Abcc1-4, Abcb1, and Abcg2 were elevated in NASH livers, whereas Abcc2 and Abcb1 were not properly localized to the membrane, similar to that previously observed in human NASH. NASH rodents receiving 40-100 mg/kg MTX exhibited hepatocellular damage followed by initiation of repair, whereas damage was absent in controls. NASH rodents receiving 100 mg/kg MTX exhibited slightly greater renal toxicity, indicating multiple organ toxicity, despite the majority of the dose being excreted by 6 h. Intestinal toxicity in NASH however, was strikingly less severe than controls, and coincided with reduced fecal MTX excretion. Because MTX-induced gastrointestinal toxicity limits the dose escalation necessary for cancer remission, these data suggest a greater risk for life-threatening MTX-induced hepatic and renal toxicity in NASH in the absence of overt gastrointestinal toxicity.
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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.