Dihydroquercetin (Taxifolin) and Other Flavonoids as Inhibitors of Free Radical Formation at Key Stages of Apoptosis

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Yu. A. Vladimirov^1*, E. V. Proskurnina¹, E. M. Demin¹, N. S. Matveeva², O. B. Lubitskiy², A. A. Novikov², D. Yu. Izmailov¹, A. N. Osipov², V. P. Tikhonov³, and V. E. Kagan⁴

¹Faculty of Basic Medicine, Lomonosov Moscow State University, Lomonosovskii pr. 31, Bld. 5, 117192 Moscow, Russia; fax: (495) 147-5508; E-mail: yuvlad@mail.ru

²Russian State Medical University, ul. Ostrovityanova 1, 117997 Moscow, Russia; E-mail: anosipov@yahoo.com

³Moscow Plant “Diod”, ul. Derbenevskaya 11a, 113114 Moscow, Russia; fax: (495) 235-3777; E-mail: info@diod.ru

⁴University of Pittsburgh, 100 Technology Dr., Suite 333, 15260 Pittsburgh, PA, USA; E-mail: vkagan@ceoh.pitt.edu

^* To whom correspondence should be addressed.

Received December 20, 2007; Revision received July 12, 2008

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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 µM, 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 µM, 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 µM.

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KEY WORDS: dihydroquercetin, antioxidants, apoptosis, free-radical reactions, cytochrome c, cardiolipin

DOI: 10.1134/S00062979090092

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