دورية أكاديمية
CYP2E1 mediated advanced oxidation protein products exacerbate acetaminophen induced drug-derived liver injury in vitro and in vivo.
| العنوان: | CYP2E1 mediated advanced oxidation protein products exacerbate acetaminophen induced drug-derived liver injury in vitro and in vivo. |
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| المؤلفون: | Xun T; Department of Pharmacy, Shenzhen Hospital, Southern Medical University, Shenzhen, China., Zhang M; Department of Pharmacy, Shenzhen Hospital, Southern Medical University, Shenzhen, China., Wei S; Department of Pharmacy, Shenzhen Hospital, Southern Medical University, Shenzhen, China., Zhao C; Department of Pharmacy, Shenzhen Hospital, Southern Medical University, Shenzhen, China., Lin Z; Department of Pharmacy, Shenzhen Hospital, Southern Medical University, Shenzhen, China., Feng H; Department of Neurology, Shenzhen Institute of Translational Medicine, Shenzhen Second People's Hospital. Shenzhen University, Shenzhen, China., Wang X; Department of Pharmacy, Shenzhen Longhua District Central Hospital, Shenzhen, China., Zhao J; Department of Pharmacy, Shenzhen Hospital, Southern Medical University, Shenzhen, China., Yang X; Department of Pharmacy, Shenzhen Hospital, Southern Medical University, Shenzhen, China. Electronic address: yaxx@smu.edu.cn. |
| المصدر: | European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences [Eur J Pharm Sci] 2024 Sep 01; Vol. 200, pp. 106829. Date of Electronic Publication: 2024 Jun 10. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science B.V Country of Publication: Netherlands NLM ID: 9317982 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0720 (Electronic) Linking ISSN: 09280987 NLM ISO Abbreviation: Eur J Pharm Sci Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Amsterdam : Elsevier Science B.V Original Publication: Amsterdam ; New York : Elsevier, c1993- |
| مواضيع طبية MeSH: | Acetaminophen*/adverse effects , Acetaminophen*/toxicity , Cytochrome P-450 CYP2E1*/metabolism , Chemical and Drug Induced Liver Injury*/metabolism , Chemical and Drug Induced Liver Injury*/etiology , Advanced Oxidation Protein Products*/metabolism, Animals ; Humans ; Male ; Liver/drug effects ; Liver/metabolism ; Liver/pathology ; Renal Insufficiency, Chronic/chemically induced ; Renal Insufficiency, Chronic/metabolism ; Mice, Inbred C57BL ; Hep G2 Cells ; Mice ; Cell Line |
| مستخلص: | Drug-induced liver injury (DILI) is prevalent in the treatment of chronic kidney disease (CKD). Advanced oxidation protein products (AOPPs) are markers of CKD progression and participate in the occurrence and development of liver diseases. However, the mechanisms underlying the regulation of DILI in CKD have not been established. Herein, we demonstrate the involvement of Cytochrome p450 2E1 (CYP2E1) in DILI induced by AOPPs is exacerbated by exposure to acetaminophen (APAP). We used a adenine-induced CKD model, a model of DILI induced by APAP, and the AOPPs model was generated by intraperitoneal injection. The decline in renal function was associated with a significantly increased concentration of Scr, BUN and AOPPs, and renal tissue fibrosis. The ALT, AST, and AOPPs levels and liver tissue necrosis increased significantly in CKD model group compared with the sodium carboxymethyl cellulose (CMCNa) group. In the AOPPs model, compared to the PBS controls, ALT, AST, and AOPP levels, and liver tissue necrosis increased significantly. In HepG2 or L0-2 cell lines, cell survival was significantly reduced in the AOPP + APAP treatment and CYP2E1 protein expression was increased. FPS-ZM1 or NAC attenuated the hepatocyte toxicity induced by AOPP + APAP and suppression of CYP2E1 expression. AOPPs exacerbated APAP-induced DILI through CYP2E1 signaling pathways. Protein uremic toxins, such as AOPPs, can modify drug toxicity in patients with CKD. This study provides new a rationale to reduce the generation of DILIs in clinical treatment in patients with CKD. AOPPs targeting may present a novel approach to reduce the occurrence of DILI. Competing Interests: Conflicts of interest None of the authors have a conflict of interest regarding the present study or have anything to disclose. (Copyright © 2024. Published by Elsevier B.V.) |
| فهرسة مساهمة: | Keywords: AOPPs; APAP; CKD; CYP2E1 |
| المشرفين على المادة: | 362O9ITL9D (Acetaminophen) EC 1.14.13.- (Cytochrome P-450 CYP2E1) 0 (Advanced Oxidation Protein Products) |
| تواريخ الأحداث: | Date Created: 20240612 Date Completed: 20240728 Latest Revision: 20240728 |
| رمز التحديث: | 20240729 |
| DOI: | 10.1016/j.ejps.2024.106829 |
| PMID: | 38866111 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1879-0720 |
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| DOI: | 10.1016/j.ejps.2024.106829 |