ArticleMolecular pharmaceutics2018
Nonalcoholic Fatty Liver Disease and Diabetes Are Associated with Decreased CYP3A4 Protein Expression and Activity in Human Liver.
Article in Molecular pharmaceutics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 2 of them syntheses that pooled it.
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Who cites it
57 citing papers in PubMed, 2 syntheses or guidelines pooled it, 114 citations in OpenAlex.
- Clinically important alterations in pharmacogene expression in histologically severe nonalcoholic fatty liver disease.Nature communications · 2023Pooled it
- A Physiologically Based Pharmacokinetic Model to Predict the Impact of Metabolic Changes Associated with Metabolic Associated Fatty Liver Disease on Drug Exposure.International journal of molecular sciences · 2022Pooled it
- NLRP3 Inhibitor KBD3536 Attenuates Acute Inflammation, Radiation-Induced Skin Injury, and Early Metabolic Dysfunction in Preclinical Models.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Fatty acid-activated proton transporter SR4 prevents hepatic steatosis and metabolic alterations in diabetic mice by improving mitochondria function, energy balance and oxidative stress.Experimental and therapeutic medicine · 2026Article
- Effects of TNF-α in Human Precision-Cut Liver Slices and its Implications for Metabolic Dysfunction-Associated Steatohepatitis Progression.Inflammation · 2026Article
- Impact of Obesity and MASH on Zonal Hepatocellular Statin Exposure: Pharmacodynamic Insights From a Permeability-Limited Multicompartment Liver Model.CPT: pharmacometrics & systems pharmacology · 2026Article
- Comparative Proteomics of Hepatocytes And Hepatic Cell Lines Using Swath-MS Reveals Significant Variations In Proteins Involved In Energy, Lipid, And Xenobiotic Metabolism.Current drug metabolism · 2026Article
- Multiomics Analysis of Liver Molecular Dysregulation Leading to Nonviral-Related Hepatocellular Carcinoma Development.Journal of proteome research · 2025Article
- Liver-specific actions of GH and IGF1 that protect against MASLD.Nature reviews. Endocrinology · 2025 · on this mapReview
- Transcriptomic and Proteomics Analysis of a Lipid-Loaded HepaRG Model for Steatosis Reveals Altered Regulation in Lipid and Xenobiotic Metabolism.Current drug metabolism · 2025Article
- Prevalence of polypharmacy and associated side effects in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD): a systematic review and meta-analysis.BMJ nutrition, prevention & health · 2025Article
- Pharmacovigilance of Drug-Drug Interactions with Nirmatrelvir/Ritonavir.Infectious diseases and therapy · 2024Article
- Dynamic pattern of postprandial bile acids in paediatric non-alcoholic fatty liver disease.Liver international : official journal of the International Association for the Study of the Liver · 2024Article
- Impact of obesity and roux-en-Y gastric bypass on the pharmacokinetics of (R)- and (S)-omeprazole and intragastric pH.CPT: pharmacometrics & systems pharmacology · 2024Article
- Decoding the Role of CYP450 Enzymes in Metabolism and Disease: A Comprehensive Review.Biomedicines · 2024Review
- Jingzhi Guanxin Oral Liquids Attenuate Atherosclerotic Coronary Heart Disease via Modulating Lipid Metabolism and PPAR-Related Targets.Pharmaceuticals (Basel, Switzerland) · 2024Article
- E4bp4-Cyp3a11 axis in high-fat diet-induced obese mice with weight fluctuation.Nutrition & metabolism · 2024Article
- Article
- In Vitro to In Vivo Scalars for Drug Clearance in Nonalcoholic Fatty Liver and Steatohepatitis.Drug metabolism and disposition: the biological fate of chemicals · 2024Article
- Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease in the Western population. We investigated the association of nonalcoholic fatty liver disease (NAFLD) and diabetes mellitus on CYP3A4 activity in human liver tissue from brain dead donors ( n = 74). Histopathologically graded livers were grouped into normal ( n = 24), nonalcoholic fatty liver (NAFL, n = 26), and nonalcoholic steatohepatitis (NASH, n = 24) categories. The rate of conversion of midazolam to its 1-hydroxy metabolite was used to assess in vitro CYP3A4 activity in human liver microsomes (HLM). A proteomics approach was utilized to quantify the protein expression of CYP3A4 and related enzymes. Moreover, a physiologically based pharmacokinetic (PBPK) model was developed to allow prediction of midazolam concentration in NAFL and NASH livers. CYP3A4 activity in NAFL and NASH was 1.9- and 3.1-fold ( p < 0.05) lower than normal donors, respectively. Intrinsic clearance (CLint) was 2.7- ( p < 0.05) and 4.1-fold ( p < 0.01) lower in donors with NAFL and NASH, respectively. CYP3A4 protein expression was significantly lower in NAFL and NASH donors ( p < 0.05) and accounted for significant midazolam hydroxylation variability in a multiple linear regression analysis (β = 0.869, r
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