{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T12:07:56Z","timestamp":1789646876876,"version":"4.0.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T00:00:00Z","timestamp":1708646400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Valproic acid (VPA) has been widely used as an antiepileptic drug for decades. Although VPA is effective and well-tolerated, long-term VPA treatment is usually associated with hepatotoxicity. However, the underlying mechanisms of VPA-caused hepatotoxicity remain unclear. In this study, a total of 157 pediatric patients with epilepsy were recruited and divided into normal liver function (NLF, 112 subjects) group and abnormal liver function (ABLF, 45 subjects) group. We observed that <jats:italic>MTHFR<\/jats:italic> A1298C and <jats:italic>MTHFR<\/jats:italic> C677T variants may be linked to VPA-induced liver dysfunction (<jats:italic>p<\/jats:italic> = 0.001; <jats:italic>p<\/jats:italic> = 0.023, respectively). We also found that the <jats:italic>MTHFR<\/jats:italic> A1298C polymorphism was associated with a higher serum Hcy level (<jats:italic>p<\/jats:italic> = 0.001) and a lower FA level (<jats:italic>p<\/jats:italic> = 0.001). Moreover, the serum Hcy levels was strongly correlated with the GSH and TBARS concentrations (r = \u22120.6065, <jats:italic>P<\/jats:italic> &amp;lt; 0.001; r = 0.6564, <jats:italic>P<\/jats:italic> &amp;lt; 0.001, respectively). Furthermore, logistic analysis indicated that <jats:italic>MTHFR<\/jats:italic> A1298C\/C677T polymorphisms and increased Hcy concentrations may be risk factors for VPA-induced liver dysfunction. These results suggested that individual susceptibility to VPA-induced liver dysfunction may result from <jats:italic>MTHFR<\/jats:italic> A1298C\/C677T polymorphisms and increased Hcy levels. This study may be helpful for the prevention and guidance of VPA-induced liver dysfunction.<\/jats:p>","DOI":"10.3389\/fphar.2024.1358262","type":"journal-article","created":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T04:38:32Z","timestamp":1708663112000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Associations between one-carbon metabolism and valproic acid-induced liver dysfunction in epileptic patients"],"prefix":"10.3389","volume":"15","author":[{"given":"Jingwei","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaotong","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinbo","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangdong","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhimei","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhua","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linfeng","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,2,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1016\/s0920-1211(02)00153-5","article-title":"The effect of B-vitamins on hyperhomocysteinemia in patients on antiepileptic drugs","volume":"51","author":"Apeland","year":"2002","journal-title":"Epilepsy Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1080\/03602530600959433","article-title":"Oxidative stress as a mechanism of valproic acid-associated hepatotoxicity","volume":"38","author":"Chang","year":"2006","journal-title":"Drug Metab. 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