دورية أكاديمية
أعرض في EDS

Different ethanol exposure durations affect cytochrome P450 2E1-mediated sevoflurane metabolism in rat liver.

التفاصيل البيبلوغرافية
العنوان: Different ethanol exposure durations affect cytochrome P450 2E1-mediated sevoflurane metabolism in rat liver.
المؤلفون: Jiang W; Department of Anesthesiology, School of Clinical Medicine of North Sichuan Medical College, Nanchong, 637000, Sichuan, China., Zhang M; Department of Anesthesiology, School of Clinical Medicine of North Sichuan Medical College, Nanchong, 637000, Sichuan, China., Cao R; Department of Anesthesiology, School of Clinical Medicine of North Sichuan Medical College, Nanchong, 637000, Sichuan, China., Wang X; Department of Anesthesiology, School of Clinical Medicine of North Sichuan Medical College, Nanchong, 637000, Sichuan, China., Zuo Y; Department of Anesthesiology, School of Clinical Medicine of North Sichuan Medical College, Nanchong, 637000, Sichuan, China. zuoyb2519@163.com.; Department of Anesthesiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, Sichuan, China. zuoyb2519@163.com.
المصدر: BMC anesthesiology [BMC Anesthesiol] 2024 Sep 10; Vol. 24 (1), pp. 321. Date of Electronic Publication: 2024 Sep 10.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 100968535 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2253 (Electronic) Linking ISSN: 14712253 NLM ISO Abbreviation: BMC Anesthesiol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : BioMed Central, 2001-
مواضيع طبية MeSH: Sevoflurane* , Cytochrome P-450 CYP2E1*/metabolism , Rats, Sprague-Dawley* , Ethanol*/administration & dosage , Ethanol*/pharmacology , Liver*/metabolism , Liver*/drug effects , Anesthetics, Inhalation* , Methyl Ethers*, Animals ; Male ; Rats ; Time Factors
مستخلص: Background: Chronic alcohol users often exhibit an increased minimum alveolar concentration (MAC) of sevoflurane, yet the specific mechanism remains unclear. It has been reported that ethanol exposure can upregulate the protein expression and enzyme activity of cytochrome P450 2E1 (CYP2E1). CYP2E1 is a key enzyme that converts 2-5% of sevoflurane into equimolar amounts of hexafluoroisopropanol (HFIP) and F - . This study aims to explore whether ethanol exposure could alter sevoflurane metabolism through CYP2E1 modulation, potentially explaining the increased MAC observed in alcohol users.
Methods: Eighty adult male Sprague-Dawley (SD) rats were randomly divided into two groups and received either 50% ethanol (dose: 3 g/kg) or 0.9% saline twice daily by gavage. After 1, 2, 3, and 4 weeks of gavage, ten rats were randomly selected from each group to undergo 1-hour anesthesia with 2.3% sevoflurane. Blood samples were collected after anesthesia to measure the concentration of free HFIP using gas chromatography. Additionally, the left lobe tissue of the liver was collected for the analysis of CYP2E1 protein expression by Western blot and CYP2E1 enzyme activity by colorimetric assay. Correlations between these parameters were analyzed using Pearson's correlation.
Results: In the ethanol group, CYP2E1 expression, activity, and the concentration of free HFIP were significantly higher at all time points compared to the control group (P < 0.05), except for protein expression in the first week (P > 0.05). Within-group comparisons indicated no significant changes in any of the parameters for the control group (P > 0.05). In the ethanol group, there was no difference in free HFIP concentration between the first and second weeks (P > 0.05), but a significant increase was observed in the third and fourth weeks (P < 0.01); protein expression and enzyme activity significantly varied over time, especially showing a notable increase from the first to the third and fourth weeks (P < 0.05). Correlation analysis revealed strong positive correlations between free HFIP concentration and CYP2E1 activity (r = 0.7898), free HFIP concentration and CYP2E1 expression (r = 0.8418), and CYP2E1 activity and expression (r = 0.8740), all with P < 0.001.
Conclusions: Ethanol exposure increased both the expression and enzymatic activity of CYP2E1, consequently enhancing the metabolism of sevoflurane.
(© 2024. The Author(s).)
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فهرسة مساهمة: Keywords: CYP2E1; Ethanol; Hexafluoroisopropanol (HFIP); Inhalation anesthesia; Sevoflurane
المشرفين على المادة: 38LVP0K73A (Sevoflurane)
EC 1.14.13.- (Cytochrome P-450 CYP2E1)
3K9958V90M (Ethanol)
0 (Anesthetics, Inhalation)
0 (Methyl Ethers)
تواريخ الأحداث: Date Created: 20240910 Date Completed: 20240911 Latest Revision: 20240914
رمز التحديث: 20240914
مُعرف محوري في PubMed: PMC11384694
DOI: 10.1186/s12871-024-02704-5
PMID: 39256673
قاعدة البيانات: MEDLINE
الوصف
تدمد:1471-2253
DOI:10.1186/s12871-024-02704-5