ArticleOncotarget2015
Identification of cytochrome CYP2E1 as critical mediator of synergistic effects of alcohol and cellular lipid accumulation in hepatocytes in vitro.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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.
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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.
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Who cites it
15 citing papers in PubMed, 31 citations in OpenAlex.
- Acute Acetaminophen Hepatotoxicity And Platelet Dysfunction.Journal of medical toxicology : official journal of the American College of Medical Toxicology · 2025Article
- Pathogenesis of Alcoholic Fatty Liver a Narrative Review.Life (Basel, Switzerland) · 2023Review
- Autophagy, Oxidative Stress, and Alcoholic Liver Disease: A Systematic Review and Potential Clinical Applications.Antioxidants (Basel, Switzerland) · 2023Review
- Xenobiotic-Induced Aggravation of Metabolic-Associated Fatty Liver Disease.International journal of molecular sciences · 2022Review
- Oxidative Stress-A Key Player in the Course of Alcohol-Related Liver Disease.Journal of clinical medicine · 2021Review
- Comparison of gene expression and biotransformation activity of HepaRG cells under static and dynamic culture conditions.Scientific reports · 2021Article
- The History of Alcoholic Liver Disease: From an Unrecognized Disease to One of the Most Frequent Diseases in Hepatology.Journal of clinical medicine · 2021Review
- Experimental models of metabolic and alcoholic fatty liver disease.World journal of gastroenterology · 2021Review
- Dietary Thiols: A Potential Supporting Strategy against Oxidative Stress in Heart Failure and Muscular Damage during Sports Activity.International journal of environmental research and public health · 2020Review
- Ethanol-induced CYP2E1 Expression is Reduced by Lauric Acid via PI3K Pathway in HepG2 Cells.Tropical life sciences research · 2020Article
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- Iso-alpha acids from hops (Humulus lupulus) inhibit hepatic steatosis, inflammation, and fibrosis.Laboratory investigation; a journal of technical methods and pathology · 2018Article
- Oxidative stress: role of physical exercise and antioxidant nutraceuticals in adulthood and aging.Oncotarget · 2018Review
- Chronic Intermittent Hypoxia Causes Lipid Peroxidation and Altered Phase 1 Drug Metabolizing Enzymes in the Neonatal Rat Liver.Reactive oxygen species (Apex, N.C.) · 2017Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clinical studies propose a causative link between the consumption of alcohol and the development and progression of liver disease in obese individuals. However, it is incompletely understood how alcohol and obesity interact and whether the combined effects are additive or synergistic. In this study, we developed an in vitro model to address this question. Lipid accumulation in primary human hepatocytes was induced by incubation with oleic acid. Subsequently, steatotic and control hepatocytes were incubated with up to 50 mM alcohol. This alcohol concentration on its own revealed only minimal effects but significantly enhanced oleate-induced lipogenesis and cellular triglyceride content compared to control cells. Similarly, lipid peroxidation, oxidative stress and pro-inflammatory gene expression as well as CYP2E1 levels and activity were synergistically induced by alcohol and steatosis. CYP2E1 inhibition blunted these synergistic pathological effects. Notably, alcohol and cellular steatosis also induced autophagy in a synergistic manner, and also this was mediated via CYP2E1. Further induction of autophagy ameliorated the joint effects of alcohol and oleic acid on hepatocellular lipid accumulation and inflammatory gene expression while inhibition of autophagy further enhanced the dual pathological effects. Further analyses revealed that the joint synergistic effect of alcohol and steatosis on autophagy was mediated via activation of the JNK-pathway. In summary, our data indicate that alcohol induces not only pathological but also protective mechanisms in steatotic hepatocytes via CYP2E1. These findings may have important implications on the prognosis and treatment of alcoholic liver disease particularly in obese individuals.
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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.