Dihydroquercetin (taxifolin) and other flavonoids as inhibitors of free radical formation at key stages of apoptosis.
Formation of free radicals in mitochondria plays a key role in the development of apoptosis, which includes formation of superoxide by the respiratory chain, formation of radicals by cytochrome c-cardiolipin complex in the presence of hydrogen peroxide or lipids, and chain lipid peroxidation resulting in cytochrome c release from mitochondria and initiation of the apoptotic cascade. In this work the effect of taxifolin (dihydroquercetin) and some other antioxidants on these three radical-producing reactions was studied. Peroxidase activity of the complex of cytochrome c with dioleyl cardiolipin estimated by chemiluminescence with luminol decreased by 50% with quercetin, taxifolin, rutin, Trolox, and ionol at concentrations 0.7, 0.7, 0.8, 3, and 10 microM, respectively. The lipid radical production detected by coumarin C-525-activated chemiluminescence decreased under the action of rutin and taxifolin in a dose-dependent manner, so that a 50% inhibition of chemiluminescence was observed at the antioxidant concentrations of 3.7 and 10 microM, respectively. Thus, these two radical-producing reactions responsible for apoptosis onset are inhibited by antioxidants at rather low concentrations. Experiments performed on liver slices and mash showed that taxifolin, quercetin, naringenin, and Trolox have low inhibitory effect on the lucigenin-dependent chemiluminescence in the tissue only at concentrations higher than 100 microM.
Faculty of Basic Medicine, Lomonosov Moscow State University, Bld. 5, 117192 Moscow, Russia. yuvlad@mail.ru
Yu A
YA
Vladimirov
E V
EV
Proskurnina
E M
EM
Demin
N S
NS
Matveeva
O B
OB
Lubitskiy
A A
AA
Novikov
D Yu
DY
Izmailov
A N
AN
Osipov
V P
VP
Tikhonov
V E
VE
Kagan
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002839:Chromans / Q000737:chemistry / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D005609:Free Radicals / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015394:Molecular Structure; D009195:Peroxidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D011794:Quercetin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D012431:Rutin / Q000737:chemistry / Q000494:pharmacology; D013481:Superoxides / Q000037:antagonists & inhibitors / Q000378:metabolism
D000975:Antioxidants; D002839:Chromans; D005419:Flavonoids; D005609:Free Radicals; D013481:Superoxides; D012431:Rutin; D045304:Cytochromes c; D011794:Quercetin; C003377:taxifolin; D009195:Peroxidase; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid