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Prooxidant activity of fisetin: effects on energy metabolism in the rat liver.

机译:非瑟酮的抗氧化活性:对大鼠肝脏能量代谢的影响。

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摘要

Flavonols, which possess the B-catechol ring, as quercetin, are capable of producing o-hemiquinones and to oxidize NADH in a variety of mammalian cells. The purpose of this study was to investigate whether fisetin affects the liver energy metabolism and the mitochondrial NADH to NAD+ ratio. The action of fisetin on hepatic energy metabolism was investigated in the perfused rat liver and isolated mitochondria. In isolated mitochondria, fisetin decreased the respiratory control and ADP/O ratios with the substrates alpha-ketoglutarate and succinate. In the presence of ADP, respiration of isolated mitochondria was inhibited with both substrates, indicating an inhibitory action on the ATP-synthase. The stimulation of the ATPase activity of coupled mitochondria and the inhibition of NADH-oxidase activity pointed toward a possible uncoupling action and the interference of fisetin with mitochondrial energy transduction mechanisms. In livers from fasted rats, fisetin inhibited ketogenesis from endogenous sources. The beta-hydroxybutyrate/ acetoacetate ratio, which reflects the mitochondrial NADH/NAD+ redox ratio, was also decreased. In addition, fisetin (200 muM) increased the production of (14)CO2 from exogenous oleate. The results of this investigation suggest that fisetin causes a shift in the mitochondrial redox potential toward a more oxidized state with a clear predominance of its prooxidant activity.
机译:具有B-邻苯二酚环的黄酮醇,如槲皮素,能够在多种哺乳动物细胞中产生邻半醌,并能氧化NADH。这项研究的目的是调查非瑟定是否会影响肝脏能量代谢以及线粒体NADH与NAD +的比率。在灌注的大鼠肝脏和分离的线粒体中研究了非瑟定对肝能量代谢的作用。在分离的线粒体中,非瑟汀与底物α-酮戊二酸酯和琥珀酸酯降低了呼吸控制和ADP / O的比率。在ADP的存在下,两种底物都抑制了分离的线粒体的呼吸作用,表明对ATP合酶具有抑制作用。对偶合线粒体ATPase活性的刺激和对NADH氧化酶活性的抑制,表明可能的解偶联作用以及非瑟酮对线粒体能量转导机制的干扰。在禁食大鼠的肝脏中,非瑟汀抑制内源性酮的生成。反映线粒体NADH / NAD +氧化还原比的β-羟基丁酸酯/乙酰乙酸酯比率也降低了。此外,非瑟汀(200μM)增加了来自外源油酸酯的(14)CO2的产量。这项研究的结果表明,非瑟定会导致线粒体氧化还原电势向更氧化的状态转变,并具有明显的前氧化活性。

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