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Effect of ketone treatment and glycolysis inhibition in brain cancer cells (U87MG) and rat primary cultured neurons exposed to hyperbaric oxygen and amyloid beta
Author(s) -
Bennett Angela,
Ari Csilla,
Kesl Shan,
Luke Jaimie,
Diamond David,
Dean Jay,
D'Agostino Dominic
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.822.8
Subject(s) - superoxide , ketone bodies , neuroprotection , pharmacology , viability assay , reactive oxygen species , ketogenic diet , oxidative stress , chemistry , glycolysis , amyloid beta , ketosis , apoptosis , biochemistry , medicine , endocrinology , metabolism , enzyme , diabetes mellitus , peptide , psychiatry , epilepsy
Mild ketosis from caloric restriction or the ketogenic diet confers a therapeutic effect against a wide range of pathologies, including brain cancer and Alzheimer's disease. Based on previous work, we hypothesized that supplemental ketones, glycolysis inhibition (lonidamine) and hyperbaric oxygen (HBO) would decrease viability of U87 MG cells. Furthermore, we hypothesized that ketones would prevent oxidative stress in primary neurons associated with amyloid beta (Ab) toxicity and HBO. LDH assays were used to measure cell viability in response to ketones (1–10mM), lonidamine (glycolysis inhibitor) and HBO (3atm, 60 min.) Rat primary neurons were treated with 10nM Aβ42 for 24 hours (with and without HBO) and superoxide anion production was measured with dihydroethidium (DHE). Lonidamine and HBO increased U87 MG cell death in cultures exposed to acute drug treatment (1hr). Ketone treatment in primary neurons decreased superoxide anion production by 20.5% and 36.2% in normobaric treatment (NBO) and HBO, respectively. Ketone treatment in Aβ42 treated neurons reduced superoxide by 23% and 16.5% in NBO and HBO, respectively. We conclude that glycolysis inhibition decreases viability in U87 MG cells and that supplemental ketones reduce superoxide production in primary rat neurons exposed to HBO and Aβ. These observations support a therapeutic effect of ketones in brain cancer and Alzheimer's disease.