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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 diolmetabolites, epoxidemetabolites, ketonemetabolites, 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. Abbreviations: α-MSH: alpha-melanocyte-stimulating hormone; AA: arachidonic acid; BDNF: brain-derived neurotrophic factor; CGRP: calcitonin gene-related peptide; COX: cycloxygenase; CYP4A: cytochrome P450 oxidase 4A; DiHOME: dihydroxy-octadecenoic acid; EF: electric field; EIA: enzyme immunoassay; ELISA: enzymelinked immunosorbent assay; EpOME: epoxy-octadecenoic acid; GPR: G protein-coupled receptor; HELP: high-voltage electric potential; HETE: hydroxyeicosatetraenoic acid; HODE: hydroxyoctadecadienoic acid; HOTrE: hydroxyoctadecatrienoic acid; HpODE: hydroperoxyoctadecadienoic acid; LA: linoleic acid; LC-MS/MS: liquid chromatography in combination with tandem mass spectrometry; LOX: lipoxygenase; NGF: nerve growth factor; OEA: oleoylethanolamide; OxoODE: oxo-octadecadienoic acid; PG: prostaglamdin; 15-PGDH: 15-hydroxy prostaglandin dehydrogenase; PLA2: phospholipase A2; PLA2G2D: group IID secretory phospholipase A2; PPAR-γ: peroxisome proliferator-activated receptor-gamma: SP: substance P; TRPV1: transient receptor potential vanilloid 1; and VIP: vasoactive intestinal peptide

integrative molecular medicine

Acute exposure to an electric field induces changes in human plasma 9-HODE, 13-HODE, and immunoreactive substance P levels: Insight into the molecular mechanisms of electric field therapy