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. Thc LDCL activity was reduced by 16 % and 42 % following thc addition of 1 mM 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.