ArticleLaboratory investigation; a journal of technical methods and pathology2021
Advanced oxidation protein products downregulate CYP1A2 and CYP3A4 expression and activity via the NF-κB-mediated signaling pathway in vitro and in vivo.
Article in Laboratory investigation; a journal of technical methods and pathology, 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, 19 citations in OpenAlex.
- Pharmacokinetics, safety, and dose optimization of GST-HG171 in renal impairment: insights from physiologically based pharmacokinetic modeling.Antimicrobial agents and chemotherapy · 2026Trial
- Deciphering cytochrome P450 reductase role in MASLD: molecular mechanisms and pathophysiological implications.Nature reviews. Gastroenterology & hepatology · 2026Review
- Development of machine learning-based multi-task quantitative structure-activity relationship models for predicting toxicities in six human organ systems.Computational toxicology (Amsterdam, Netherlands) · 2026Article
- Metabolic disruption in salmonids following co-exposure to road runoff contaminants 6PPD-Quinone and 9,10-anthraquinone.The Science of the total environment · 2026Article
- Cytochrome P450 (CYP) 1 enzymes in acute lung injury: from molecular insights to therapeutic implications.Redox report : communications in free radical research · 2025Review
- Serum Concentration of Apixaban in Relation to Renal Function in Older Hospitalized Patients.Drugs & aging · 2025Observational
- Effect of Severe Renal Impairment on Dordaviprone (ONC201) Pharmacokinetics.Drugs in R&D · 2025Article
- Quality Control of Shenqi Tongmai Oral Liquid Based on Quantitative Analysis of Multicomponents by Single Marker, Molecular Docking, and Multivariate Statistics.Phytochemical analysis : PCA · 2025Article
- How Uremic Toxins Alter Atorvastatin Disposition: Molecular Mechanisms of Inhibition of the Enzyme CYP3A4.Balkan medical journal · 2025Article
- Recent advances in gut microbiota metabolite regulation of hepatic pregnane X receptor.Frontiers in immunology · 2025Review
- Advanced Oxidative Protein Products Had a Diagnostic Accuracy for Identifying Chronic Kidney Disease in Adult Population.Metabolites · 2024Article
- Gut microbiota trigger host liver immune responses that affect drug-metabolising enzymes.Frontiers in immunology · 2024Review
- Inflammatory signaling on cytochrome P450-mediated drug metabolism in hepatocytes.Frontiers in pharmacology · 2022Review
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7 authors at 2 institutions in 1 country.
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Abstract
Uremic toxin accumulation is one possible reason for alterations in hepatic drug metabolism in patients with chronic kidney disease (CKD). However, the types of uremic toxins and underlying mechanisms are poorly understood. In this study, we report the role of advanced oxidation protein products (AOPPs), a modified protein uremic toxin, in the downregulation of cytochromes P450 1A2 (CYP1A2) and P450 3A4 (CYP3A4) expression levels and activities. We found that AOPP accumulation in plasma in a rat CKD model was associated with decreased protein levels of CYP1A2 and CYP3A4. CYP1A2 and CYP3A4 metabolites (acetaminophen and 6β-hydroxytestosterone, respectively,) in liver microsomes were also significantly decreased. In human hepatocytes, AOPPs significantly decreased CYP1A2 and CYP3A4 protein levels in a dose- and time-dependent manner and downregulated their activities; however, bovine serum albumin (BSA), a synthetic precursor of AOPPs, had no effect on these parameters. The effect of AOPPs was associated with upregulation of p-IKKα/β, p-IκBα, p-NF-κB, and inflammatory cytokines protein levels and increases in p-IKKα/β/IKKα, p-IκBα/IκBα, and p-NF-κB/NF-κB phosphorylation ratios. Further, NF-kB pathway inhibitors BAY-117082 and PDTC abolished the downregulatory effects of AOPPs. These findings suggest that AOPPs downregulate CYP1A2 and CYP3A4 expression and activities by increasing inflammatory cytokine production and stimulating NF-κB-mediated signaling. Protein uremic toxins, such as AOPPs, may modify the nonrenal clearance of drugs in patients with CKD by influencing metabolic enzymes.
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