新药物GEPC的抗氧化和促氧化分析:ESR光谱法检测及其对脂质过氧化和生物分子降解的保护作用。

J Liu, A Mori, K Ogata
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引用次数: 0

摘要

l -抗坏血酸2-(20 β -11-氧-齐墩-12-烯-29-酸乙酯-3- β -酰基磷酸氢)钠盐(GEPC)是一种新合成的甘草酸乙酯和抗坏血酸的磷酸二酯键化合物。在本研究中,我们发现GEPC能有效抑制Fe(III)-ADP/ nadph诱导的肝微粒体过氧化。其抑制作用远大于甘草酸(GA),与抗坏血酸的刺激作用形成对比。一项ESR研究表明,GEPC似乎具有抗坏血酸清除DPPH和超氧化物自由基的巨大损失。然而,与抗坏血酸一样,GEPC抑制了Fe(II)-H2 O2和Cr(VI)-H2 O2体系中羟基自由基的产生。与抗坏血酸不同,GEPC没有促氧化作用,在ESR研究或铁诱导脱氧核糖和DNA降解实验中,它是一种有效的铁螯合剂。GEPC对羟基自由基诱导的某些生物分子(如碳水化合物、氨基酸和DNA)的降解具有保护作用,进一步证明了其清除羟基自由基的作用。这些结果表明,GEPC除了具有抗坏血酸自氧化和提高GA的水溶性的保护作用外,还具有抗坏血酸的抗氧化作用,虽然不如GA强,但比GA强。
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Antioxidant and pro-oxidant assay for a new drug GEPC: detected by ESR spectrometry and by protective effects on lipid peroxidation and biomolecule degradation.

L-Ascorbic acid 2-(20 beta-11-oxo-olean-12-en-29-oic acid ethylester-3-beta-yl hydrogen phosphate) sodium salt (GEPC) is a newly synthesized compound representing a phosphate diester linkage of glycyrrhetic acid ethylester and ascorbic acid. In the present study, we found that GEPC effectively inhibited Fe(III)-ADP/NADPH-induced peroxidation of liver microsomes. The inhibitory effect was much greater than that of glycyrrhetic acid (GA), and contrasted with the stimulatory effect of ascorbic acid. An ESR study showed that GEPC appeared to have a great loss of the DPPH and superoxide radical scavenging effects of ascorbic acid. However, GEPC, like ascorbic acid, inhibited hydroxyl radicals generation in both Fe(II)-H2 O2 and Cr(VI)-H2 O2 systems. GEPC, unlike ascorbic acid, showed no pro-oxidant effect and acted as an effective iron-chelating agent in the ESR study or in the iron-induced deoxyribose and DNA degradation assays. The hydroxyl radical scavenging effect of GEPC was further demonstrated by its protective effect on the hydroxyl radical- induced degradation of certain biomolecules, i.e., carbohydrates, amino acids, and DNA. These results demonstrate that beside its protective effect on ascorbic acid autoxidation and increasing water solubility of GA, GEPC is also an antioxidant though not so powerful as ascorbic acid but more powerful than GA.

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