Association between serum trace element concentrations and valproic acid-induced hepatotoxicity in pediatric patients with epilepsy

Linfeng Ma; Qi Liu; Li Chen; Xiaoni Kong; Jingwei Zhu; Zhe Wang; Dan Wang

doi:10.36721/PJPS.2025.38.2.REG.14006.1

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Association between serum trace element concentrations and valproic acid-induced hepatotoxicity in pediatric patients with epilepsy

Author(s)

Linfeng Ma Department of Medicine, Shandong College of Traditional Chinese Medicine,Yantai, Shandong,China

Qi Liu Department of Medicine, Shandong College of Traditional Chinese Medicine,Yantai, Shandong,China

Li Chen Department of Medicine, Shandong College of Traditional Chinese Medicine,Yantai, Shandong,China

Xiaoni Kong Department of Medicine, Shandong College of Traditional Chinese Medicine,Yantai, Shandong,China

Jingwei Zhu Department of Clinical Laboratory, Qingdao University Medical College Affiliated Yantai Yuhuangding Hospital,Yantai, Shandong,China

Zhe Wang Department of Clinical Laboratory, Qingdao University Medical College Affiliated Yantai Yuhuangding Hospital,Yantai, Shandong,China

Dan Wang Department of Pharmacy, Shandong College of Traditional Chinese Medicine,Yantai, Shandong,China

Abstract

Valproic acid (VPA), a commonly used antiepileptic drug, may cause hepatotoxicity during its clinical use. However, the mechanisms underlying VPA-associated hepatotoxicity remain unclear. In this study, 137 age-matched epileptic patients receiving long-term VPA treatment were enrolled, and the blood samples were collected for liver function, trace element concentrations and oxidative stress tests. The results revealed that patients with VPA-induced hepatotoxicity had higher concentrations of iron (Fe, P ? 0.001), and lower concentrations of cobalt (Co) and selenium (Se) than those in the control group (P = 0.036 and P ? 0.001, respectively). In addition, multiple regression analysis indicated that the Fe concentration was positively associated with transferase activities and oxidative stress parameters (glutathione and thiobarbituric acid-reactive substances, P ? 0.05), while the concentrations of Co and Se were negatively correlated with transferase activities and oxidative stress parameters (P ? 0.05). Moreover, logistic regression analysis indicated that the Fe concentration was correlated with a greater risk for hepatotoxicity (P = 0.001, OR: 2.387), whereas the concentrations of Co (P = 0.038, OR: 0.889) and Se (P = 0.001, OR: 0.813) were negatively correlated with VPA-associated hepatotoxicity. These results clarified that certain trace elements (Fe, Co and Se) may contribute to the pathogenesis of VPA-associated hepatotoxicity via the oxidative stress pathway.

Publication Details

Page(s) 333-341

DOI 10.36721/PJPS.2025.38.2.REG.14006.1

Published Journal: Pakistan Journal of Pharmaceutical Sciences, Volume: 38, Issue: 1, Year: 2025

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Keywords

Epilepsy, Hepatotoxicity, trace elements, Pediatric patients, Valproic acid

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