Ketosis (acetoacetate) can generate oxygen radicals and cause increased lipid peroxidation and growth inhibition in human endothelial cells

Elevated level of cellular lipid peroxidation can increase the incidence of vascular disease. The mechanism by which ketosis causes accelerated cellular damage and vascular disease in diabetes is not known. This study was undertaken to test the hypothesis that elevated levels of ketone bodies increa...

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Bibliographic Details
Published in:Free radical biology & medicine 1998-12, Vol.25 (9), p.1083-1088
Main Authors: Jain, Sushil K., Kannan, Krishnaswamy, Lim, Gideon
Format: Article
Language:English
Subjects:
3-Hydroxybutyric Acid - metabolism
Acetoacetates - metabolism
Cell Division - drug effects
Cells, Cultured
Cytochrome c Group - metabolism
Diabetes
Diabetes Mellitus - physiopathology
Endothelial cells
Endothelium, Vascular - metabolism
Free radical
Humans
Ketosis
Ketosis - metabolism
Lipid Peroxidation
Metals - pharmacology
Reactive Oxygen Species - metabolism
Superoxide Dismutase - metabolism
Superoxides - metabolism
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Summary:Elevated level of cellular lipid peroxidation can increase the incidence of vascular disease. The mechanism by which ketosis causes accelerated cellular damage and vascular disease in diabetes is not known. This study was undertaken to test the hypothesis that elevated levels of ketone bodies increase lipid peroxidation in endothelial cells. Human umbilical venous endothelial cells (HUVEC) were cultured for 24 h at 37 oC with ketone bodies (acetoacetate, β-hydroxybutyrate). Acetoacetate, but not β-hydroxybutyrate, caused an increase in lipid peroxidation and growth inhibition in cultured HUVEC. To determine whether ketone bodies generate oxygen radicals, studies using cell-free buffered solution were performed. They showed a significant superoxide dismutase (SOD) inhibitable reduction of cytochrome C by acetoacetate, but not by β-hydroxybutyrate, suggesting the generation of superoxide anion radicals by acetoacetate. Additional studies show that Fe 2+ potentiates oxygen radical generation by acetoacetate. Thus, elevated levels of ketone body acetoacetate can generate oxygen radicals and cause lipid peroxidation in endothelial cells, providing a possible mechanism for the increased incidence of vascular disease in diabetes.
ISSN:0891-5849
1873-4596
DOI:10.1016/S0891-5849(98)00140-3