ArticleFree radical biology & medicine2012
Alcohol steatosis and cytotoxicity: the role of cytochrome P4502E1 and autophagy.
Article in Free radical biology & medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 93 citations in OpenAlex.
- Roles of Oxidative Stress and Autophagy in Alcohol-Mediated Brain Damage.Antioxidants (Basel, Switzerland) · 2025Review
- Mechanism and regulation of mitophagy in liver diseases: a review.Frontiers in cell and developmental biology · 2025Review
- Autophagy, Oxidative Stress, and Alcoholic Liver Disease: A Systematic Review and Potential Clinical Applications.Antioxidants (Basel, Switzerland) · 2023Review
- Associations between Liver Enzymes, Lifestyle Risk Factors and Pre-Existing Medical Conditions in a Population-Based Cross-Sectional Sample.Journal of clinical medicine · 2023Article
- Scutellarin prevents acute alcohol-induced liver injury via inhibiting oxidative stress by regulating the Nrf2/HO-1 pathway and inhibiting inflammation by regulating the AKT, p38 MAPK/NF-κB pathways.Journal of Zhejiang University. Science. B · 2023Article
- Autophagy in liver diseases.World journal of hepatology · 2021Review
- Immunological mechanisms and therapeutic targets of fatty liver diseases.Cellular & molecular immunology · 2021Review
- Ethanol-induced CYP2E1 Expression is Reduced by Lauric Acid via PI3K Pathway in HepG2 Cells.Tropical life sciences research · 2020Article
- Autophagy, Metabolism, and Alcohol-Related Liver Disease: Novel Modulators and Functions.International journal of molecular sciences · 2019Review
- Diverse Consequences in Liver Injury in Mice with Different Autophagy Functional Status Treated with Alcohol.The American journal of pathology · 2019Article
- Lipophagy and Alcohol-Induced Fatty Liver.Frontiers in pharmacology · 2019Review
- Babao Dan attenuates acute ethanol-induced liver injury via Nrf2 activation and autophagy.Cell & bioscience · 2019Article
- Role and mechanisms of autophagy in alcohol-induced liver injury.Advances in pharmacology (San Diego, Calif.) · 2019Review
- Alcohol-induced autophagy via upregulation of PIASy promotes HCV replication in human hepatoma cells.Cell death & disease · 2018Article
- Promotion of autophagosome-lysosome fusionRSC advances · 2018Article
- Impairment of Akt activity by CYP2E1 mediated oxidative stress is involved in chronic ethanol-induced fatty liver.Redox biology · 2018Article
- Cytochrome P450s and Alcoholic Liver Disease.Current pharmaceutical design · 2018Review
- Relevance of autophagy to fatty liver diseases and potential therapeutic applications.Amino acids · 2017Review
- Review
- Ginsenosides from stems and leaves of ginseng prevent ethanol-induced lipid accumulation in human L02 hepatocytes.Chinese journal of integrative medicine · 2017Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The goal of the current study was to evaluate whether CYP2E1 plays a role in binge-ethanol induced steatosis and if autophagy impacts CYP2E1-mediated hepatotoxicity, oxidative stress and fatty liver formation produced by ethanol. Wild type (WT), CYP2E1 knockin (KI) and CYP2E1 knockout (KO) mice were gavaged with 3g/kg body wt ethanol twice a day for four days. This treatment caused fatty liver, elevation of CYP2E1 and oxidative stress in WT and KI mice but not KO mice. Autophagy was impaired in ethanol-treated KI mice compared to KO mice as reflected by a decline in the LC3-II/LC3-I ratio and lower total LC-3 and Beclin-1 levels coupled to increases in P62, pAKT/AKT and mTOR. Inhibition of macroautophagy by administration of 3-methyladenine enhanced the binge ethanol hepatotoxicity, steatosis and oxidant stress in CYP2E1 KI, but not CYP2E1 KO mice. Stimulation of autophagy by rapamycin blunted the elevated steatosis produced by binge ethanol. Treatment of HepG2 E47 cells which express CYP2E1 with 100mM ethanol for 8 days increased fat accumulation and oxidant stress but decreased autophagy. Ethanol had no effect on these reactions in HepG2 C34 cells which do not express CYP2E1. Inhibition of autophagy elevated ethanol toxicity, lipid accumulation and oxidant stress in the E47, but not C34 cells. The antioxidant N-acetylcysteine, and CYP2E1 inhibitor chlormethiazole blunted these effects of ethanol. These results indicate that CYP2E1 plays an important role in binge ethanol-induced fatty liver. We propose that CYP2E1-derived reactive oxygen species inhibit autophagy, which subsequently causes accumulation of lipid droplets. Inhibition of autophagy promotes binge ethanol induced hepatotoxicity, steatosis and oxidant stress via CYP2E1.
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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.