Potential biomarker of fibroblast growth factor 21 in valproic acid‐treated livers

Abstract

Background Valproic acid (VPA) is a clinical medicine primarily prescribed to control epileptic symptoms. VPA has potential side‐effects, such as hepatotoxicity. Fibroblast growth factor 21 (FGF21) is a functional cytokine for metabolic regulation. In this article, we aimed to evaluate the possible clinical application of FGF21 in VPA‐treated livers in early undetected liver injury (EULI). Methods Methodologically, plasma samples of VPA‐treated epileptic patients were isolated for biochemical and high‐performance liquid chromatography tests. In addition, VPA‐dosed mice were subjected to determinations of serological parameters, key regulatory effectors and FGF21 expressions through biochemical analyses, enzyme‐linked immunosorbent assay, immunohistochemistry stain, immunofluorescence stain, and reverse transcription‐polymerase chain reaction (RT‐PCR) test, respectively. Results The serological data suggested that VPA‐treated epileptic patients showed visibly elevated FGF21 contents in plasma samples. However, other diagnostic parameters showed inconspicuous changes. As revealed in animal study, VPA‐dosed mice exhibited undetected morphological alterations and hormonal changes in the liver, pancreas, and kidneys. Furthermore, serological parameters and key regulatory proteins in VPA‐dosed livers and controls showed inconspicuous changes. Interestingly, endogenous FGF21 expressions in VPA‐dosed mice were increased in sera. In further experiments, the findings showed that intracellular expressions of FGF21 mRNA and protein were upregulated in VPA‐dosed livers as revealed in RT‐PCR and immunoassay. Conclusions Taken together, these preliminary data reveal that functional FGF21 cytokine may serve as a potent predictor in VPA‐related EULI.

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Effects of Sodium Valproate Monotherapy on Blood Liver Enzyme Levels in Patients with Epilepsy: A Meta-Analysis

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