Abstract
: Valproic acid (VPA) is a commonly used drug for treating epilepsy and other neurological and psychiatric disorders. Drug-induced liver injury (DILI) caused by VPA has been reported in several studies. MicroRNAs (miRNAs) are recognized as potent regulators involved in many biological processes and are currently considered promising biomarkers for detecting DILI. The aim of the present study was to evaluate the expression levels of two hepato-specific microRNAs, miR-122 and miR-155, in hepatocytes exposed to VPA. This study was conducted using HepG2 cell lines treated with different concentrations of VPA for 24, 48, 72, 96, and 120 hours. The results showed that exposure to VPA significantly elevated the transcription levels of both tested miRNAs in HepG2 cell lines after 24 hours. However, prolonged exposure down-regulated the expression levels of these miRNAs, possibly due to VPA-induced cell death. We suggest that the significant decrease in miRNA expression in treated cells is correlated with VPA-induced apoptosis, followed by enhanced cell death after 120 hours of VPA exposure. Our findings imply that miR-122 and miR-155 play an important role in valproic acid detoxification and have prognostic or therapeutic implications.
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