Medical treatment using high-voltage electric potential (HELP) devices to generate an electric field (EF) is an alternative therapy commonly used in Japan. However, the underlying mechanisms of the potential health benefits are not fully understood. To address this issue, we performed plasma lipidomics using liquid chromatography in combination with tandem mass spectrometry (LC-MS/MS). 9-Hydroxyoctadecadienoic acid (HODE), 13-HODE, and 13-hydroperoxy-octadecadienoic acid (HpODE) levels were significantly upregulated after HELP (18 kV, 30 min) exposure. However, there was no effect on HODE-related diol-metabolites, epoxidemetabolites, ketone-metabolites, or prostaglandins (PGs). We further examined the effect of HELP exposure on plasma concentrations of mediators using enzymelinked immunosorbent assay (ELISA)/enzyme immunoassay (EIA). Immunoreactive substance P (SP) and brain-derived neurotrophic factor (BDNF) levels were significantly upregulated after HELP exposure. Under these conditions, HELP exposure had no effect on immunoreactive levels of vasoactive intestinal peptide (VIP), bradykinin, calcitonin gene-related peptide (CGRP), or motilin. Our findings provide insight into the possible relationship between the pharmacological modulation of neuromediators and that of HODEs by EF exposure. They may also be important in the development of electroceuticals.

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