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

IF 3.8 3区 化学 Q2 CHEMISTRY, MULTIDISCIPLINARY
Frontiers in Chemistry Pub Date : 2025-05-13 eCollection Date: 2025-01-01 DOI:10.3389/fchem.2025.1509785
Qian Zhu, Xuefeng Xie, Ling Fang, Cheng Huang, Jun Li
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引用次数: 0

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.

慢性酒精摄入破坏酒精性脂肪性肝病的细胞色素P450酶活性:代谢改变和治疗靶点的见解
酒精性脂肪性肝病(AFLD)是慢性饮酒的常见后果,其特征是肝脏中的脂质积累和氧化应激。细胞色素P450 (CYP450)酶在代谢酒精和其他化合物中起重要作用。然而,酒精对这些酶的具体长期影响尚不清楚。方法:采用大鼠AFLD模型,观察长时间乙醇暴露对CYP450活性和表达的影响。关键酶如CYP2E1、CYP2D6和CYP3A1与脂质积累和氧化应激的关系进行了评估。结果:CYP2E1、CYP2D6和CYP3A1的表达和活性显著改变,与肝脏脂质积累和氧化应激增加有关。此外,p -糖蛋白(P-gp)表达升高,提示慢性酒精摄入可能影响药物运输和排泄。讨论:这些发现为AFLD的分子机制提供了新的见解,并强调了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。
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来源期刊
Frontiers in Chemistry
Frontiers in Chemistry Chemistry-General Chemistry
CiteScore
8.50
自引率
3.60%
发文量
1540
审稿时长
12 weeks
期刊介绍: Frontiers in Chemistry is a high visiblity and quality journal, publishing rigorously peer-reviewed research across the chemical sciences. Field Chief Editor Steve Suib at the University of Connecticut is supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to academics, industry leaders and the public worldwide. Chemistry is a branch of science that is linked to all other main fields of research. The omnipresence of Chemistry is apparent in our everyday lives from the electronic devices that we all use to communicate, to foods we eat, to our health and well-being, to the different forms of energy that we use. While there are many subtopics and specialties of Chemistry, the fundamental link in all these areas is how atoms, ions, and molecules come together and come apart in what some have come to call the “dance of life”. All specialty sections of Frontiers in Chemistry are open-access with the goal of publishing outstanding research publications, review articles, commentaries, and ideas about various aspects of Chemistry. The past forms of publication often have specific subdisciplines, most commonly of analytical, inorganic, organic and physical chemistries, but these days those lines and boxes are quite blurry and the silos of those disciplines appear to be eroding. Chemistry is important to both fundamental and applied areas of research and manufacturing, and indeed the outlines of academic versus industrial research are also often artificial. Collaborative research across all specialty areas of Chemistry is highly encouraged and supported as we move forward. These are exciting times and the field of Chemistry is an important and significant contributor to our collective knowledge.
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