Chou Tien-min, Greenspan Phillip
Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602-2356, USA.
Biochim Biophys Acta. 2002 Mar 15;1581(1-2):57-63. doi: 10.1016/s1388-1981(02)00119-1.
Myeloperoxidase, in the presence of hydrogen peroxide and nitrite, promotes the lipid peroxidation of low density lipoprotein (LDL); the modified lipoprotein is then capable of being readily endocytosed by macrophages. Since acetaminophen has been shown to inhibit the leukocyte myeloperoxidase antimicrobial system and is, under certain experimental conditions, an antioxidant, the effect of acetaminophen on the myeloperoxidase-hydrogen peroxide-nitrite mediated oxidation of LDL was examined. The content of LDL lipid hydroperoxides after incubation with 50 nM myeloperoxidase, 100 microM nitrite and a hydrogen peroxide generating system for 6 h was reduced by approx. 80% in the presence of 25-250 microM acetaminophen. The production of thiobarbituric acid-reactive substances was also inhibited by acetaminophen to a similar extent. Acetylsalicylic acid (25-100 microM) did not inhibit LDL lipid peroxidation mediated by the myeloperoxidase enzyme system. LDL, treated with myeloperoxidase, hydrogen peroxide and nitrite for 14 h, was metabolized by macrophages to a much greater extent than native LDL. The presence of acetaminophen prevented the modification of LDL; the lipoprotein was metabolized by macrophages to the same extent as was native LDL. These results demonstrate that acetaminophen is a potent inhibitor of the myeloperoxidase-hydrogen peroxide-nitrite mediated modification of LDL.
在过氧化氢和亚硝酸盐存在的情况下，髓过氧化物酶会促进低密度脂蛋白（LDL）的脂质过氧化；随后，这种修饰后的脂蛋白能够被巨噬细胞轻易地内吞。由于对乙酰氨基酚已被证明可抑制白细胞髓过氧化物酶抗菌系统，并且在某些实验条件下是一种抗氧化剂，因此研究了对乙酰氨基酚对髓过氧化物酶 - 过氧化氢 - 亚硝酸盐介导的LDL氧化的影响。在与50 nM髓过氧化物酶、100 microM亚硝酸盐和一个过氧化氢生成系统孵育6小时后，LDL脂质氢过氧化物的含量在存在25 - 250 microM对乙酰氨基酚的情况下降低了约80%。硫代巴比妥酸反应性物质的产生也被对乙酰氨基酚以类似程度抑制。乙酰水杨酸（25 - 100 microM）并未抑制髓过氧化物酶酶系统介导的LDL脂质过氧化。用髓过氧化物酶、过氧化氢和亚硝酸盐处理14小时的LDL，被巨噬细胞代谢的程度比天然LDL大得多。对乙酰氨基酚的存在可防止LDL的修饰；该脂蛋白被巨噬细胞代谢的程度与天然LDL相同。这些结果表明，对乙酰氨基酚是髓过氧化物酶 - 过氧化氢 - 亚硝酸盐介导的LDL修饰的有效抑制剂。
