Kapiotis Stylianos, Hermann Marcela, Exner Markus, Laggner Hilde, Gmeiner Bernhard M K
Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Austria
Free Radic Res. 2005 Nov;39(11):1193-202. doi: 10.1080/10715760500138981.
The oxidative modification of LDL may play an important role in the early events of atherogenesis. Thus the identification of antioxidative compounds may be of therapeutic and prophylactic importance regarding cardiovascular disease. Copper-chlorophyllin (Cu-CHL), a Cu(2+)-protoporphyrin IX complex, has been reported to inhibit lipid oxidation in biological membranes and liposomes. Hemin (Fe(3+)-protoporphyrin IX) has been shown to bind to LDL thereby inducing lipid peroxidation. As Cu-CHL has a similar structure as hemin, one may assume that Cu-CHL may compete with the hemin action on LDL. Therefore, in the present study Cu-CHL and the related compound magnesium-chlorophyllin (Mg-CHL) were examined in their ability to inhibit LDL oxidation initiated by hemin and other LDL oxidizing systems. LDL oxidation by hemin in presence of H(2)O(2) was strongly inhibited by both CHLs. Both chlorophyllins were also capable of effectively inhibiting LDL oxidation initiated by transition metal ions (Cu(2+)), human umbilical vein endothelial cells (HUVEC) and tyrosyl radicals generated by myeloperoxidase (MPO) in presence of H(2)O(2) and tyrosine. Cu- and Mg-CHL showed radical scavenging ability as demonstrated by the diphenylpicrylhydracylradical (DPPH)-radical assay and estimation of phenoxyl radical generated diphenyl (dityrosine) formation. As assessed by ultracentrifugation the chlorophyllins were found to bind to LDL (and HDL) in serum. The present study shows that copper chlorophyllin (Cu-CHL) and its magnesium analog could act as potent antagonists of atherogenic LDL modification induced by various oxidative stimuli. As inhibitory effects of the CHLs were found at concentrations as low as 1 mumol/l, which can be achieved in humans, the results may be physiologically/therapeutically relevant.
低密度脂蛋白（LDL）的氧化修饰可能在动脉粥样硬化形成的早期事件中起重要作用。因此，鉴定抗氧化化合物对于心血管疾病的治疗和预防可能具有重要意义。铜叶绿素（Cu-CHL），一种Cu（2+）-原卟啉IX复合物，已被报道可抑制生物膜和脂质体中的脂质氧化。血红素（Fe（3+）-原卟啉IX）已被证明可与LDL结合，从而诱导脂质过氧化。由于Cu-CHL与血红素结构相似，人们可能认为Cu-CHL可能与血红素对LDL的作用竞争。因此，在本研究中，研究了Cu-CHL和相关化合物镁叶绿素（Mg-CHL）抑制由血红素和其他LDL氧化系统引发的LDL氧化的能力。在H（2）O（2）存在下，血红素引发的LDL氧化受到两种叶绿素的强烈抑制。两种叶绿素也能够有效抑制由过渡金属离子（Cu（2+））、人脐静脉内皮细胞（HUVEC）以及在H（2）O（2）和酪氨酸存在下髓过氧化物酶（MPO）产生的酪氨酰自由基引发的LDL氧化。通过二苯基苦味酰基自由基（DPPH）自由基测定和对二苯醚自由基（二酪氨酸）形成的苯氧基自由基估计表明，Cu-CHL和Mg-CHL具有自由基清除能力。通过超速离心评估发现，叶绿素与血清中的LDL（和HDL）结合。本研究表明，铜叶绿素（Cu-CHL）及其镁类似物可作为由各种氧化刺激诱导的动脉粥样硬化性LDL修饰的有效拮抗剂。由于在低至1μmol/l的浓度下发现了叶绿素的抑制作用，而这一浓度在人体内是可以达到的，因此该结果可能具有生理/治疗相关性。
