Boersma Brenda J, D'Alessandro Tracy, Benton Matthew R, Kirk Marion, Wilson Landon S, Prasain Jeevan, Botting Nigel P, Barnes Stephen, Darley-Usmar Victor M, Patel Rakesh P
Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL 35294-2180, USA.
Free Radic Biol Med. 2003 Dec 1;35(11):1417-30. doi: 10.1016/j.freeradbiomed.2003.08.009.
Soy isoflavones and other polyphenolics have a number of potentially important beneficial effects on the pro-oxidant aspects of chronic inflammation. The impact of inflammatory cell-specific metabolism of polyphenolics, which can include halogenation and nitration, on the properties of these compounds has not been examined. Using either human neutrophils or differentiated human leukemia cells (HL-60) stimulated with phorbol ester to elicit a respiratory burst, the hypothesis that local generation of reactive oxygen and nitrogen species may metabolize and modify the biological properties of the soy isoflavones was examined. Coincubation of the stimulated cells with genistein or daidzein had no effect on the respiratory burst. Medium from stimulated cells in the presence of the isoflavones and NO(2)(-) increased the inhibition of copper-induced LDL oxidation. Mass spectrometry analysis of this medium revealed that monochlorinated, dichlorinated, and nitrated isoflavones, formed through a myeloperoxidase-dependent mechanism, were present. The consumption of genistein in the presence of cells was both extensive and rapid with > 95% of the genistein converted to either the chlorinated or nitrated metabolites within 30 min. Chemically synthesized 3'-chlorogenistein and 3'-chlorodaidzein increased the inhibition of LDL oxidation by approximately 4-fold and 2-fold over genistein and daidzein, respectively. These results lead to the hypothesis that inflammatory cell-specific metabolism of polyphenolics can modify the properties of these compounds at the local site of inflammation.
大豆异黄酮和其他多酚类物质对慢性炎症的促氧化方面具有许多潜在的重要有益作用。多酚类物质在炎症细胞中的特异性代谢（包括卤化和硝化）对这些化合物性质的影响尚未得到研究。利用佛波酯刺激的人中性粒细胞或分化的人白血病细胞（HL-60）引发呼吸爆发，检验了活性氧和氮物种的局部产生可能代谢并改变大豆异黄酮生物学性质的假说。将刺激后的细胞与染料木黄酮或大豆苷元共同孵育对呼吸爆发没有影响。在存在异黄酮和NO₂⁻的情况下，来自刺激细胞的培养基增强了对铜诱导的低密度脂蛋白氧化的抑制作用。对该培养基的质谱分析表明，存在通过髓过氧化物酶依赖性机制形成的单氯代、二氯代和硝化异黄酮。在有细胞存在的情况下，染料木黄酮的消耗既广泛又迅速，在30分钟内超过95%的染料木黄酮转化为氯代或硝化代谢产物。化学合成的3'-氯代染料木黄酮和3'-氯代大豆苷元分别比染料木黄酮和大豆苷元对低密度脂蛋白氧化的抑制作用增加了约4倍和2倍。这些结果引出了一个假说，即多酚类物质在炎症细胞中的特异性代谢可以在炎症局部改变这些化合物的性质。
