Histone Deacetylase (HDAC) Expression Changes in the White Blood Cells of Sodium Valproate Treated Patients and Their Association with Obesity

Background: Sodium valproate (NaV) is a widely prescribed antiepileptic and mood-stabilizing drug that also functions as a histone deacetylase inhibitor (HDACi). HDAC deregulation contributes to cancer and neurodegenerative disorders, yet the feedback regulation of HDAC genes under pharmaceutical inhibition remains unclear. Methods: This pilot study evaluated mRNA expression of class I HDACs (HDAC1, HDAC2, HDAC3, HDAC8) and class IIa HDACs (HDAC4, HDAC5, HDAC7, HDAC9) using RT-qPCR in peripheral blood from 50 NaV-treated epileptic patients and 50 age/sex-matched neurological controls. Results: NaV treatment was associated with significant upregulation of HDAC1 (↑2.6-fold) and HDAC3 (↑2.1-fold), alongside downregulation of HDAC7 (↓1.9-fold). HDAC2 expression was unaffected by NaV but significantly reduced in smokers across groups. Obesity was linked to increased HDAC1 and reduced HDAC3 and HDAC9 expression. Conclusions: NaV therapy induces distinct de novo expression changes in HDAC genes, suggesting feedback regulation mechanisms. These findings provide a basis for larger studies examining HDAC superfamily expression as potential biomarkers of treatment response