ArticleClinics and research in hepatology and gastroenterology2021
Cytochrome P450 2E1 should not be neglected for acetaminophen-induced liver injury in metabolic diseases with altered insulin levels or glucose homeostasis.
Article in Clinics and research in hepatology and gastroenterology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 24 citations in OpenAlex.
- Epigenetic Biomarkers of Transition from Metabolically Healthy Obesity to Metabolically Unhealthy Obesity Phenotype: A Prospective Study.International journal of molecular sciences · 2021Trial
- Vitamin K1 attenuates acetaminophen-induced ferroptotic hepatic damage in mice via targeting keap1/Nrf2/HO-1 pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Quercetin-liposomes effectively regulated the Nrf2/Keap1 and NF-κB/P38 MAPK signaling pathways and protected the liver against paracetamol-induced damage.Journal, genetic engineering & biotechnology · 2025Article
- Astragaloside IV as a promising therapeutic agent for liver diseases: current landscape and future perspectives.Frontiers in pharmacology · 2025Review
- A Review: Cytochrome P450 in Alcoholic and Non-Alcoholic Fatty Liver Disease.Diabetes, metabolic syndrome and obesity : targets and therapy · 2024Review
- Molecular Mechanism Pathways of Natural Compounds for the Treatment of Non-Alcoholic Fatty Liver Disease.Molecules (Basel, Switzerland) · 2023Review
- Label-Free Imaging Techniques to Evaluate Metabolic Changes Caused by Toxic Liver Injury in PCLS.International journal of molecular sciences · 2023Article
- Acetaminophen-Induced Hepatotoxicity in Obesity and Nonalcoholic Fatty Liver Disease: A Critical Review.Livers · 2023Article
- Stress mechanism involved in the progression of alcoholic liver disease and the therapeutic efficacy of nanoparticles.Frontiers in immunology · 2023Review
- Review
- Xenobiotic-Induced Aggravation of Metabolic-Associated Fatty Liver Disease.International journal of molecular sciences · 2022Review
- Review
- CYP2E1 in Alcoholic and Non-Alcoholic Liver Injury. Roles of ROS, Reactive Intermediates and Lipid Overload.International journal of molecular sciences · 2021Review
- Review
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acetaminophen (APAP) hepatotoxicity is mediated by N-acetyl-p-benzoquinone imine (NAPQI), a highly toxic metabolite generated by cytochrome P450 2E1 (CYP2E1). Thus, pathological conditions increasing CYP2E1 activity can favour APAP-induced liver injury, which is characterized by massive hepatocellular necrosis and secondary sterile inflammation. In a recent work, Wang et al. showed that APAP-induced hepatotoxicity was exacerbated in a murine model of type 1 diabetes induced by the administration of streptozotocin (STZ). Higher hepatotoxicity was in particular associated with a stronger proinflammatory response of the resident macrophages. Although the authors carried out numerous investigations, they did not study hepatic CYP2E1, nor discussed the possible role of this enzyme in the exacerbation of APAP hepatotoxicity. However, numerous investigations reported hepatic CYP2E1 induction in STZ-treated rodents, which could be secondary to insulinopenia and ketosis. This commentary also discusses the role of insulin resistance in CYP2E1 induction observed in obesity and nonalcoholic fatty liver disease. Investigators studying APAP-induced liver injury in the context of insulinopenia or hyperinsulinemia are thus encouraged to consider CYP2E1 as a significant player in the observed phenotypic changes.
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