ArticleBiomedicine & pharmacotherapy = Biomedecine & pharmacotherapie2022
CYP450 drug inducibility in NAFLD via an in vitro hepatic model: Understanding drug-drug interactions in the fatty liver.
Article in Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 27 citations in OpenAlex.
- Hepatic steatosis affects the outcome of anti-tuberculosis treatment in pulmonary tuberculosis patients.Journal of clinical tuberculosis and other mycobacterial diseases · 2026Article
- Hepatic Steatosis: A Pandemic Disease Causing Serious Secondary Diseases.Deutsches Arzteblatt international · 2026Review
- Hepatocyte Models for Metabolic Dysfunction-Associated Steatotic Liver Disease: A Comparative Analysis of Non-HepG2 Cell Models.International journal of molecular sciences · 2026Review
- PPARγ mediated enhanced lipid biogenesis fuelseLife · 2025Article
- Article
- Organic cation transporter 1 and cytochrome P450s play crucial roles in coptisine- and worenine-induced hepatotoxicity.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Metabolic Dysfunction-Associated Steatotic Liver Disease Is Accompanied by Increased Activities of Superoxide Dismutase, Catalase, and Carbonyl Reductase 1 and Levels of miR-200b-3p in Mouse Models.Antioxidants (Basel, Switzerland) · 2024Article
- A Review: Cytochrome P450 in Alcoholic and Non-Alcoholic Fatty Liver Disease.Diabetes, metabolic syndrome and obesity : targets and therapy · 2024Review
- Comparative Pharmacokinetic Study of Rhubarb Anthraquinones in Normal and Nonalcoholic Fatty Liver Disease Rats.European journal of drug metabolism and pharmacokinetics · 2024Article
- Effects of short-chain per- and polyfluoroalkyl substances (PFAS) on human cytochrome P450 (CYP450) enzymes and human hepatocytes: AnCurrent research in toxicology · 2023Article
- Alterations in Cytoskeleton and Mitochondria in the Development and Reversal of Steatosis in Human Hepatocytes.Cellular and molecular gastroenterology and hepatology · 2023Article
- Could Alcohol Abuse and Dependence on Junk Foods Inducing Obesity and/or Illicit Drug Use Represent Danger to Liver in Young People with Altered Psychological/Relational Spheres or Emotional Problems?International journal of molecular sciences · 2022Review
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Drug-drug-interactions (DDIs) occur when a drug alters the metabolic rate, efficacy, and toxicity of concurrently used drugs. While almost 1 in 4 adults now use at least 3 concurrent prescription drugs in the United States, the Non-alcoholic fatty liver disease (NAFLD) prevalence has also risen over 25%. The effect of NALFD on DDIs is largely unknown. NAFLD is characterized by lipid vesicle accumulation in the liver, which can progress to severe steatohepatitis (NASH), fibrosis, cirrhosis, and hepatic carcinoma. The CYP450 enzyme family dysregulation in NAFLD, which might already alter the efficacy and toxicity of drugs, has been partially characterized. Nevertheless, the drug-induced dysregulation of CYP450 enzymes has not been studied in the fatty liver. These changes in enzymatic inducibility during NAFLD, when taking concurrent drugs, could cause unexpected fatalities through inadvertent DDIs. We have, thus, developed an in vitro model to investigate the CYP450 transcriptional regulation in NAFLD. Specifically, we cultured primary human hepatocytes in a medium containing free fatty acids, high glucose, and insulin for seven days. These cultures displayed intracellular macro-steatosis after 5 days and cytokine secretion resembling NAFLD patients. We further verified the model's dysregulation in the transcription of key CYP450 enzymes. We then exposed the NAFLD model to the drug inducers rifampicin, Omeprazole, and Phenytoin as activators of transcription factors pregnane X receptor (PXR), aryl hydrocarbon receptor (AHR) and constitutive androstane receptor (CAR), respectively. In the NAFLD model, Omeprazole maintained an expected induction of CYP1A1, however Phenytoin and Rifampicin showed elevated induction of CYP2B6 and CYP2C9 compared to healthy cultures. We, thus, conclude that the fatty liver could cause aggravated drug-drug interactions in NAFLD or NASH patients related to CYP2B6 and CYP2C9 enzymes.
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