AFMK, a melatonin metabolite, attenuates X-ray-induced oxidative damage to DNA, proteins and lipids in mice
AFMK, a melatonin metabolite, attenuates X-ray-induced oxidative damage to DNA, proteins and lipids in mice
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DOI：
10.1111/j.1600-079x.2007.00432.x
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发表时间：
2007-04-01
影响因子：
10.3
通讯作者：
Anzai, Kazunori
中科院分区：
文献类型：
--
作者：
Manda, Kailash;Ueno, Megumi;Anzai, Kazunori
褪黑激素的抗氧化功能已得到充分证实。然而，N-1-乙酰基-N-2-甲酰基-5-甲氧基犬尿胺（AFMK），褪黑激素的代谢物是一种很少研究的生物胺，特别是在其体内抗氧化功能。我们评价了X射线照射对C57 BL小鼠生物分子（DNA、蛋白质和脂质）的氧化损伤以及AFMK的预防作用。采用单细胞凝胶电泳法检测大脑皮质DNA损伤程度，酶联免疫吸附法检测血清8-羟基脱氧鸟苷（8-OHdG）水平。蛋白质和脂质的氧化修饰以大脑皮质的羰基含量和4-HAE + MDA（4-羟基烯醛+丙二醛）状态来测量。辐射暴露显着增加血清中的8-OHdG水平以及彗星尾中的DNA迁移。AFMK预处理显著抑制DNA损伤。此外，AFMK预处理可改善辐射诱导的蛋白质羰基含量和HAE + MDA的增加。小鼠全身暴露于X射线照射也降低了脑巯基含量（蛋白结合巯基，总巯基和非蛋白巯基）的水平，这是显着保护AFMK。AFMK预处理小鼠的血浆总抗氧化能力的辐射诱导的下降显着逆转。此外，AFMK显示出非常高水平的体外羟基自由基清除潜力，其通过2-羟基-5，5-二甲基-1-吡咯啉N-氧化物（DMPO-OH）加合物的电子自旋共振（ESR）研究来测量。ESR分析得出的IC 50值为338.08 nM。本研究表明，AFMK是一种有效的抗氧化剂，在体内和体外系统。
Antioxidant function of melatonin is well established. However, N-1-acetyl-N-2-formyl-5-methoxykynuramine (AFMK), a melatonin metabolite is a sparingly investigated biogenic amine, especially in relation to its in vivo antioxidant function. We have evaluated the oxidative damage to biomolecules (DNA, protein and lipid) induced by X-irradiation in C57BL mice and the prophylactic action of AFMK. The extent of DNA damage was analyzed by single-cell gel electrophoresis in cerebral cortex and serum 8-hydroxydeoxyguanosine (8-OHdG) levels by enzyme-linked immunosorbent assay. Oxidative modification of protein and lipid was measured in the terms of carbonyl content and 4-HAE + MDA (4-hydroxyalkenal + malondialdehyde) status of brain cortex. Radiation exposure dramatically augmented the level of 8-OHdG in serum as well as DNA migration in the comet tail. AFMK pretreatment significantly inhibited DNA damage. In addition, radiation-induced augmentation of protein carbonyl content and HAE + MDA was ameliorated by AFMK pretreatment. Whole-body exposure of mice to X-irradiation also reduced the level of brain sulfhydryl contents (protein-bound sulfhydryl, total sulfhydryl, and nonprotein sulfhydryl) which were significantly protected by AFMK. Radiation-induced decline in the total antioxidant capacity of plasma was significantly reversed in AFMK pretreated mice. Moreover, AFMK showed a very high level of in vitro hydroxyl radical scavenging potential which was measured by an electron spin resonance (ESR) study of the 2-hydroxy-5,5-dimethyl-1-pyrrolineN-oxide (DMPO-OH) adduct. IC50 values resulting from ESR analysis was 338.08 nM. The present study indicate that AFMK is a potent antioxidant in both in vivo and in vitro systems.