Kapiotis S, Sengoelge G, Hermann M, Held I, Seelos C, Gmeiner B M
Clinical Institute of Medical and Chemical Laboratory Diagnostics, University of Vienna, Austria.
Arterioscler Thromb Vasc Biol. 1997 Nov;17(11):2855-60. doi: 10.1161/01.atv.17.11.2855.
The oxidative modification of LDL may play a significant role in atherogenesis. Myeloperoxidase (MPO) expressed in human atherosclerotic plaques has been suggested to be operative in vivo, making LDL atherogenic. Tyrosyl radicals generated by MPO have been shown to act as physiological pro-oxidants of lipid peroxidation in LDL. Assuming that a variety of phenolic compounds are able to form phenoxyl radicals when exposed to peroxidases, we tested the ability of paracetamol, a known analgesic drug with a tyrosine-like monophenolic structure, to act as a pro-oxidant of lipid peroxidation in LDL. Spectroscopic analyses indicated that paracetamol, similar to tyrosine, could undergo peroxidase-induced phenoxyl radical formation, which was inhibited by the radical scavenger ascorbic acid as well as by heme poisons and catalase. Measurement of conjugated dienes and lipid hydroperoxides in LDL preparations exposed to MPO/H2O2 in the absence or presence of paracetamol revealed that the drug could act as a catalyst of lipid oxidation in LDL. Similar results were found when LDL oxidation was performed with activated human neutrophils, which use MPO to promote lipid peroxidation. In conclusion, the results suggest that paracetamol could act, via a phenoxyl radical, as a catalyst of LDL oxidative modification by MPO.
低密度脂蛋白（LDL）的氧化修饰可能在动脉粥样硬化形成中起重要作用。已表明在人类动脉粥样硬化斑块中表达的髓过氧化物酶（MPO）在体内发挥作用，使LDL具有致动脉粥样硬化性。MPO产生的酪氨酸自由基已被证明可作为LDL中脂质过氧化的生理性促氧化剂。假设多种酚类化合物在暴露于过氧化物酶时能够形成苯氧自由基，我们测试了对乙酰氨基酚（一种具有酪氨酸样单酚结构的已知镇痛药）作为LDL中脂质过氧化促氧化剂的能力。光谱分析表明，与酪氨酸类似，对乙酰氨基酚可发生过氧化物酶诱导的苯氧自由基形成，自由基清除剂抗坏血酸以及血红素毒物和过氧化氢酶可抑制这种形成。在不存在或存在对乙酰氨基酚的情况下，对暴露于MPO/H2O2的LDL制剂中的共轭二烯和脂质氢过氧化物的测量表明，该药物可作为LDL中脂质氧化的催化剂。当用活化的人类中性粒细胞进行LDL氧化时也发现了类似结果，活化的人类中性粒细胞利用MPO促进脂质过氧化。总之，结果表明对乙酰氨基酚可通过苯氧自由基作为MPO对LDL进行氧化修饰的催化剂。
