Mechanism of inhibitory action of ketone bodies on the production of reactive oxygen intermediates (ROIS) by polymorphonuclear leukocytes.
We determined an effect of acetoacetic acid (AcAc) and 3-hydroxybutyrate (3-OHB) on the production of reactive oxygen intermediates (ROIs) in polymorphonuclear leukocytes from healthy volunteers. Both AcAc and 3-OHB inhibited the luminol-dependent chemiluminescence (LDCL) activities assessed with initial slope and the inhibition rates were about 42%, 44% respectively by AcAc and 3-OHB when the leukocytes were preincubated with 10 mM AcAc or 3-OHB for 60 minutes. The LDCL activity was reduced by 16% and 42% following the addition of 1mM and 10 mM AcAc. The similar reduction of the LDCL activity was observed in the addition of 3-OHB. Either 3-OHB or AcAc failed to show a significant reduction of myeloperoxidase (MPO) activity. However, both 3-OHB and AcAc dose-dependently inhibited superoxide anion (O2-) production, measured by using cytochrome c. These data provided evidence that both 3-OHB and AcAc suppress neutrophil oxidative metabolism with respect with O2- production.
Sato
N
N
First Department of Internal Medicine, Gunma University School of Medicine, Maebashi, Japan.
Shimizu
H
H
Shimomura
Y
Y
Suwa
K
K
Mori
M
M
Kobayashi
I
I
D020155:3-Hydroxybutyric Acid; D000090:Acetoacetates / Q000494:pharmacology*; D000704:Analysis of Variance; D003574:Cytochrome c Group / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006885:Hydroxybutyrates / Q000494:pharmacology*; D008163:Luminescent Measurements; D008165:Luminol; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*
D000090:Acetoacetates; D003574:Cytochrome c Group; D006885:Hydroxybutyrates; D013481:Superoxides; C016635:acetoacetic acid; D008165:Luminol; D009195:Peroxidase; D020155:3-Hydroxybutyric Acid