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长期饮酒会破坏酒精性脂肪性肝病中细胞色素P450酶的活性：对代谢改变和治疗靶点的见解。

Chronic alcohol intake disrupts cytochrome P450 enzyme activity in alcoholic fatty liver disease: insights into metabolic alterations and therapeutic targets.

作者信息

Zhu Qian, Xie Xuefeng, Fang Ling, Huang Cheng, Li Jun

机构信息

Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, China.

The First Affiliated Hospital of Anhui Medical University, Hefei, China.

出版信息

Front Chem. 2025 May 13;13:1509785. doi: 10.3389/fchem.2025.1509785. eCollection 2025.

DOI:10.3389/fchem.2025.1509785
PMID:40433307
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12106329/
Abstract

INTRODUCTION

Alcoholic fatty liver disease (AFLD) is a common consequence of chronic alcohol consumption, characterized by lipid accumulation and oxidative stress in the liver. Cytochrome P450 (CYP450) enzymes play essential roles in metabolizing alcohol and other compounds. However, the specific long-term effects of alcohol on these enzymes remain unclear.

METHODS

This study the examines influence of prolonged ethanol exposure on CYP450 activity and expression in AFLD using a rat model. Key enzymes such as CYP2E1, CYP2D6, and CYP3A1 were assessed in relation to lipid accumulation and oxidative stress.

RESULTS

Significant alterations were identified in the expression and activity of CYP2E1, CYP2D6, and CYP3A1, which were associated with increased lipid accumulation and oxidative stress in the liver. Additionally, the expression of P-glycoprotein (P-gp) was elevated, suggesting that chronic alcohol intake may impact drug transport and excretion.

DISCUSSION

These findings provide new insights into the molecular mechanisms of AFLD and highlight the potential of CYP450 modulation as a therapeutic target. By elucidating how long-term ethanol exposure disrupts hepatic CYP450 enzyme profiles, this research lays the groundwork for developing personalized therapeutic strategies to improve outcomes for patients with AFLD.

摘要

引言

酒精性脂肪肝病（AFLD）是慢性饮酒的常见后果，其特征为肝脏中的脂质积累和氧化应激。细胞色素P450（CYP450）酶在酒精和其他化合物的代谢中起重要作用。然而，酒精对这些酶的具体长期影响仍不清楚。

方法

本研究使用大鼠模型研究长期乙醇暴露对AFLD中CYP450活性和表达的影响。评估了关键酶如CYP2E1、CYP2D6和CYP3A1与脂质积累和氧化应激的关系。

结果

CYP2E1、CYP2D6和CYP3A1的表达和活性出现显著变化，这与肝脏中脂质积累和氧化应激增加有关。此外，P-糖蛋白（P-gp）的表达升高，表明长期饮酒可能影响药物转运和排泄。

讨论

这些发现为AFLD的分子机制提供了新见解，并突出了CYP450调节作为治疗靶点的潜力。通过阐明长期乙醇暴露如何破坏肝脏CYP450酶谱，本研究为制定个性化治疗策略以改善AFLD患者的预后奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74ca/12106329/1aa58aa20385/fchem-13-1509785-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74ca/12106329/7ab26f93dd46/fchem-13-1509785-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74ca/12106329/2ee86af801ec/fchem-13-1509785-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74ca/12106329/40e7d52628f2/fchem-13-1509785-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74ca/12106329/845a67c6ffba/fchem-13-1509785-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74ca/12106329/23629af065ed/fchem-13-1509785-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74ca/12106329/23f6f5d04444/fchem-13-1509785-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74ca/12106329/476976bce47d/fchem-13-1509785-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74ca/12106329/f38abe68b50e/fchem-13-1509785-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74ca/12106329/1aa58aa20385/fchem-13-1509785-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74ca/12106329/7ab26f93dd46/fchem-13-1509785-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74ca/12106329/2ee86af801ec/fchem-13-1509785-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74ca/12106329/40e7d52628f2/fchem-13-1509785-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74ca/12106329/845a67c6ffba/fchem-13-1509785-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74ca/12106329/23629af065ed/fchem-13-1509785-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74ca/12106329/23f6f5d04444/fchem-13-1509785-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74ca/12106329/476976bce47d/fchem-13-1509785-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74ca/12106329/f38abe68b50e/fchem-13-1509785-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74ca/12106329/1aa58aa20385/fchem-13-1509785-g009.jpg

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