Abstract
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). 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. 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. Taken together, these preliminary data reveal that functional FGF21 cytokine may serve as a potent predictor in VPA-related EULI.
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