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Beta‐hydroxybutyrate reduces superoxide production in cultured U87 cells and hippocampal neurons: implications for metabolic therapy in cancer and CNS oxygen toxicity
Author(s) -
D'Agostino Dominic,
Kesl Shan,
Bennett Angela,
Dean Jay B
Publication year - 2011
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.25.1_supplement.832.7
Subject(s) - superoxide , hippocampal formation , reactive oxygen species , toxicity , chemistry , cancer cell , beta (programming language) , cancer research , cancer therapy , cancer , pharmacology , medicine , neuroscience , biology , biochemistry , enzyme , organic chemistry , computer science , programming language
Reactive oxygen species (ROS) are signaling molecules implicated in the etiology of numerous pathologies including CNS oxygen toxicity (seizures) and cancer growth. Ketogenic diets have a profound anticonvulsive effect and are anticipated to reduce ROS generation and thus modulate redox signaling. Ketone metabolism is highly efficient in normal brain cells, but cancer cells have impaired ketone metabolism due to mitochondrial defects. We hypothesized that beta‐hydroxybutyrate (BHB; 1–10mM) would reduce intracellular superoxide anion production in cultured rat hippocampal neurons and human U87 glioblastoma cells. Fluorescence microscopy and/or flow cytometry were used to detect real‐time intracellular superoxide production with dihydroethidium (DHE) in cultured hippocampal neurons and U87 cells. Cultures were grown in the absence or presence of BHB for 4–6 days. Results demonstrate that superoxide production (measured as fluorescence intensity units) was significantly higher (>30%) in control cells (hippocampal and U87 cells) versus BHB‐treated cells. In addition, BHB caused a dose‐dependent decrease U87 cell proliferation. These observations suggest that supplemental ketones may confer protection against CNS oxygen toxicity and malignant brain cancer through redox regulation.