How flavonoids inhibit the generation of luminol-dependent chemiluminescence by activated human neutrophils.
The mechanism by which (a panel of) flanonoids inhibit the production of luminol-dependent chemiluminescence (CLlum) by activated human neutrophils is subject to this study. CLlum is frequently used as a bio-assay to quantify the effect of xenobiotics on the production of reactive oxygen species (ROS). Most of the flavonoids decreased CLlum by inhibition of ROS production by the cells. Four selected flavonoids (Taxifolin, Eriodictyol, Hesperetin and Luteolin), inhibited myeloperoxidase (MPO) release, while two of these (Taxifolin and Eriodictyol) strongly inhibited MPO activity. Because CLlum is a MPO-dependent process these activities might mask effects of the flavonoids on ROS production. Finally, our results provide evidence that essential determinants for inhibition of O2(-)-release are the OH-groups located in the B-ring of the flavonoid molecule. Flavonoids methylated at a single OH-group in the B-ring are only inhibitory when they react with activated neutrophils in the presence of myeloperoxidase.
'T Hart
B A
BA
Dept. of Pharmacognosy, Faculty of Pharmacy, State University of Utrecht, The Netherlands.
Ip Via Ching
T R
TR
Van Dijk
H
H
Labadie
R P
RP
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000001:Calcimycin / Q000494:pharmacology; D044950:Flavanones; D005419:Flavonoids / Q000494:pharmacology*; D044948:Flavonols; D006569:Hesperidin; D006801:Humans; D008163:Luminescent Measurements; D008165:Luminol / Q000494:pharmacology*; D047311:Luteolin; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D009195:Peroxidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D011724:Pyridazines / Q000494:pharmacology*; D011794:Quercetin / Q000031:analogs & derivatives / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D044950:Flavanones; D005419:Flavonoids; D044948:Flavonols; D011724:Pyridazines; D013481:Superoxides; D000001:Calcimycin; D008165:Luminol; D011794:Quercetin; C003377:taxifolin; D006569:Hesperidin; D009195:Peroxidase; D014969:Xanthine Oxidase; D047311:Luteolin; D013755:Tetradecanoylphorbol Acetate; C007619:eriodictyol; C013015:hesperetin; D010100:Oxygen