3-Hydroxybutyrate (beta-hydroxybutyrate or 3-HBA) is small lipid-derived molecule that serves as an energy carrier during fasting, and endogenous inhibitor of histone deacetylase (HDAC). Here we report the concentrations of 3-HBA in plasma samples obtained from healthy human subjects before and after exposure to a single 30-min high-voltage electric potential (HELP) exposure using quantitative capillary electrophoresis-time-of-flight mass spectrometry (CE-TOFMS). 2-and 3-HBA were significantly upregulated after HELP exposure (4.5 kV/electrode + 4.5 kV/electrode), but not after exposure to low-strength condition (2.25 kV/electrode + 2.25 kV/electrode). There was no effect on the concentrations of 2-hydroxybutanedioate, 2-hydroxytricarballylate, 2-oxopropanoate, or ATP. Because 3-HBA is known to induce histone acetylation at the forkhead box O3a (FoxO3a) promoter, we further confirmed that FOXO3A mRNA was upregulated by 3-HBA treatment in a human epithelial colorectal adenocarcinoma Caco-2 cell line. Under these conditions stated above, 3-HBA treatment had no effect on forkhead box P3 (FOXP3) or defensin beta 132 (DEFB132) mRNA expressions. Similar changes in FOXO3A mRNA expression were obtained using sodium 4-phenylbutyrate (4-PBA) or trichostatin A (TSA) instead of 3-HBA. Our findings provide a new insight into the epigenetic mechanisms of electric field (EF) therapy.

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