Potential Suicide Prophylactic Activity by the Fish Oil Metabolite, 4-Hydroxyhexenal

• Published in: International journal of molecular sciences Vol. 23; no. 13; p. 6953
• Main Author: Kalkman, Hans O.
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.07.2022; MDPI
• Subjects: 4-hydroxyhexenal; Alzheimer's disease; Blood circulation; Coronary vessels; Docosahexaenoic acid; Emotional disorders; Fatty acids; fish oil; Fish oils; Kinases; Metabolites; Mood disorders; NRF2; Oxidation; Proteins; Suicide; suicide prevention; Suicides & suicide attempts; Transcription activation; Transcription factors
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23136953

Low levels of n-3 poly-unsaturated fatty acids (n-3 PUFAs) and high levels of n-6 PUFAs in the blood circulation are associated with an increased risk for suicide. Clinical studies indicate that docosahexaenoic acid (DHA, a n-3 PUFA found in fish-oil) displays protective effects against suicide. It has recently been proposed that the activation of the transcription factor NRF2 might be the pharmacological activity that is common to current anti-suicidal medications. Oxidation products from fish oil, including those from DHA, are electrophiles that reversibly bind to a protein ‘KEAP1’, which acts as the molecular inhibitor of NRF2 and so indirectly promotes NRF2-transcriptional activity. In the majority of publications, the NRF2-stimulant effect of DHA is ascribed to the metabolite 4-hydroxyhexenal (4HHE). It is suggested to investigate whether 4HHE will display a therapeutically useful anti-suicidal efficacy.