天然黄酮类化合物对脂氧合酶介导吩噻嗪类等药物氧化的影响

Effect of natural flavonoids on the oxidation of phenothiazines and other chemical mediated by lipoxygenase

目的研究天然黄酮类化合物茶多酚等对脂氧合酶(LOX)介导吩噻嗪类药物和异丙肾上腺素氧化反应的影响,探讨此类化合物抑制脂氧合酶协同氧化活性的可能机制。方法用分光光度法和电子自旋共振波谱仪(ESR)检测氧化反应的产物和自由基。结果大豆脂氧合酶(SLO)可介导吩噻嗪类药物氧化生成吩噻嗪阳离子自由基;天然黄酮类化合物茶多酚及其单体EGCG等可以抑制上述酶促氧化过程。SLO还可氧化异丙肾上腺素生成异丙肾上腺素红;棉子酚、DTT、GSH等酶活性调节物可抑制该氧化反应,而自由基清除剂BHA、BHT和天然黄酮类化合物茶多酚等对异丙肾上腺素红的生成没有影响。结论在本试验条件下,这些黄酮类化合物对SLO介导吩噻嗪类化合物氧化的抑制,可能主要是通过清除SLO介导外源性化学物氧化过程中产生的自由基发挥作用;此种对SLO协同氧化酶活力的抑制作用,在体内有可能减少或阻止能被LOX氧化活化产生自由基的外源化学物引起的致癌等毒作用。

Objective To investigate the effect and the possible mechanism of the natural flavonoids on the oxidation of phenothiazines and isoproterenol mediated by lipoxygenase and to probe into the possibility that the antioxidants mechanism in resisting cancer and other toxicity is exhibited by inhibiting lipoxygenase-catalyzed co-oxidation of xenobiotics.Methods The oxidation products and free radical intermediates were detected by spectrophotometry and electron spin resonance（ESR） spectrometer.Results SLO could catalyze the co-oxidation of phenothiazines to generate phenothiazine cation radicals.Natural flavonoids tea polyphenol and its monomer EGCG and other moderator could inhibit the oxidation of phenothiazines mediated by SLO.SLO could also catalyze the co-oxidation of isoproterenol to generate isoprenochrome.Gossypol,GSH,DTT could inhibit the oxidation of isoproterenol,but free radical scavenger BHA and BHT,natural flavonoids tea polyphenol and its monomer EGCG and EC,quercetin and rutin exerted no effect on the product of isoprenochrome.Conclusion It implies that the natural flavonoids inhibit the oxidation of phenothiazines to generate phenothiazines cation radicals mediated by lipoxygenase is mainly by scavenging free radicals,which is possibile to resist cancer and other toxicity of xenobiotics including phenothiazines.