中国癫痫患者丙戊酸肝毒性的预测性生物标志物：代谢物和遗传多态性的作用。

IF 3.5 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology Pub Date : 2025-07-29 DOI:10.1016/j.fct.2025.115670

Dingsheng Wen , Zhuojia Chen , Ziyi Chen , Xue Bai , Hongliang Li , Juan Chen , Qiling Dai , Guoping Zhong , Jiaming Qin , Guanzhong Ni , Min Huang , Liemin Zhou , Xueding Wang

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引用次数: 0

摘要

丙戊酸（VPA）是一种应用广泛的抗癫痫药物，但其肝毒性限制了其应用。本研究探讨了200例接受VPA单药治疗的中国癫痫患者VPA诱导肝损伤的相关生物标志物和遗传因素。我们分析了VPA及其代谢产物（4-ene-VPA、3-OH-VPA、4-OH-VPA、2-PGA）、肝功能和22个基因多态性。肝功能异常（ANLFT）患者的4-烯- vpa水平明显高于肝功能正常（NLFT）患者。CPT1A rs2228502的GG基因型与4-ene-VPA水平升高相关。ACOT1、PPARα、FFAR2、NQO1、NRF2的snp组间差异有统计学意义。Logistic回归分析发现NRF2 rs59288687和NQO1 rs10517是抗肝毒性的保护因子。总之，升高的4-烯- vpa和基因变异，包括CPT1A rs2228502、NRF2 rss59288687和NQO1 rs10517，影响肝毒性风险，为个性化治疗策略提供了见解。

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Predictive biomarkers for valproic acid-induced hepatotoxicity in Chinese patients with epilepsy: the role of metabolites and genetic polymorphisms

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Predictive biomarkers for valproic acid-induced hepatotoxicity in Chinese patients with epilepsy: the role of metabolites and genetic polymorphisms

Valproic acid (VPA) is a widely used antiepileptic drug, but its hepatotoxicity limits usage. This study explored biomarkers and genetic factors associated with VPA-induced liver injury in 200 Chinese epileptic patients on VPA monotherapy. We analyzed VPA and its metabolites (4-ene-VPA, 3-OH-VPA, 4-OH-VPA, 2-PGA), liver function, and 22 gene polymorphisms. Patients with abnormal liver function (ANLFT) had significantly higher 4-ene-VPA levels than those with normal liver function (NLFT). The GG genotype of CPT1A rs2228502 was associated with elevated 4-ene-VPA levels. SNPs in ACOT1, PPARα, FFAR2, NQO1, and NRF2 showed significant differences between groups. Logistic regression identified NRF2 rs59288687 and NQO1 rs10517 as protective factors against hepatotoxicity. In conclusion, elevated 4-ene-VPA and genetic variants, including CPT1A rs2228502, NRF2 rs59288687, and NQO1 rs10517, influence hepatotoxicity risk, providing insights for individualized treatment strategies.

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来源期刊

Food and Chemical Toxicology 工程技术-毒理学

CiteScore

10.90

自引率

4.70%

发文量

651

审稿时长

31 days

期刊介绍： Food and Chemical Toxicology (FCT), an internationally renowned journal, that publishes original research articles and reviews on toxic effects, in animals and humans, of natural or synthetic chemicals occurring in the human environment with particular emphasis on food, drugs, and chemicals, including agricultural and industrial safety, and consumer product safety. Areas such as safety evaluation of novel foods and ingredients, biotechnologically-derived products, and nanomaterials are included in the scope of the journal. FCT also encourages submission of papers on inter-relationships between nutrition and toxicology and on in vitro techniques, particularly those fostering the 3 Rs. The principal aim of the journal is to publish high impact, scholarly work and to serve as a multidisciplinary forum for research in toxicology. Papers submitted will be judged on the basis of scientific originality and contribution to the field, quality and subject matter. Studies should address at least one of the following: -Adverse physiological/biochemical, or pathological changes induced by specific defined substances -New techniques for assessing potential toxicity, including molecular biology -Mechanisms underlying toxic phenomena -Toxicological examinations of specific chemicals or consumer products, both those showing adverse effects and those demonstrating safety, that meet current standards of scientific acceptability. Authors must clearly and briefly identify what novel toxic effect (s) or toxic mechanism (s) of the chemical are being reported and what their significance is in the abstract. Furthermore, sufficient doses should be included in order to provide information on NOAEL/LOAEL values.