Chemoprotective effect of plant phenolics against anthracycline-induced toxicity on rat cardiomyocytes.: Part III.: Apigenin, baicalelin, kaempherol, luteolin and quercetin
Chemoprotective effect of plant phenolics against anthracycline-induced toxicity on rat cardiomyocytes.: Part III.: Apigenin, baicalelin, kaempherol, luteolin and quercetin
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DOI：
10.1002/ptr.1462
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发表时间：
2004-07-01
影响因子：
7.2
通讯作者：
Simánek, V
中科院分区：
文献类型：
--
作者：
Psotová, J;Chlopcíková, S;Simánek, V
类黄酮广泛存在于植物中，可作为自由基清除剂和螯合剂，具有抗炎、抗缺血、血管舒张和化学保护特性。在本研究中，在离体大鼠心脏心肌细胞、线粒体和微粒体中研究了芹菜素、黄芩素、山奈酚、木犀草素和槲皮素对阿霉素诱导的氧化应激的抗脂过氧化和细胞保护作用。将心肌细胞与测试化合物预温育1μl后，用毒性剂阿霉素(100μM，8小时)处理心肌细胞。通过细胞外 LDH 以及细胞 ADP 和 ATP 产生来评估心肌细胞保护作用。黄芩素 > 木犀草素与芹菜素 > 槲皮素 > 山奈酚的细胞保护作用呈浓度依赖性。所有测试化合物均比目前用于蒽环类抗生素治疗期间辅助治疗的右雷佐生具有更好的保护作用。在微粒体/线粒体中，槲皮素、黄芩素、山奈酚、木犀草素和芹菜素的脂质过氧化抑制的 IC50 值为 3.1 +/- 0.2/8.2 +/- 0.6、3.3 +/- 0.3/9.6 +/- 0.5、3.9 +/- 0.3/10.1 +/- 0.8、22.9 +/- 1.7/18.2 分别为+/-0.7和338.8+/-23.1/73.1+/-6.4μM。芹菜素的抗脂过氧化活性与其细胞保护作用不同，但与 2,2-二苯基-1-三硝基肼自由基的自由基清除和半峰氧化电位 (E-p/2) 相关。除心肌细胞模型外，芹菜素是所有模型中研究的黄酮类化合物中效果最差的，其心肌细胞保护作用与其他化合物相当。版权所有 (C) 2004 John Wiley Sons, Ltd.
Flavonoids are found universally in plants and act as free radical scavenging and chelating agents with anti-inflammatory, antiischemic, vasodilating and chemoprotective properties. In this study, the antilipoperoxidative and cytoprotective effects of apigenin, baicalein, kaempferol, luteolin and quercetin against doxorubic-ininduced oxidative stress were investigated in isolated rat heart cardiac myocytes, mitochondria and microsomes. After preincubation of cardiomyocytes with the test compounds for 1 It the cardiomyocytes were treated with the toxic agent, doxorubicin (100 muM for 8 h). Cardiomyocyte protection was assessed by extracellular LDH and cellular ADP and ATP production. Cytoprotection was concentration dependent for baicalein > luteolin congruent to apigenin > quercetin > kaempferol. All test compounds had significantly better protective effects than dexrazoxan, an agent currently used for adjuvant therapy during anthracycline antibiotic therapy. In microsomes/ mitochondria the IC50 values of lipid peroxidation inhibition for quercetin, baicalein, kaempferol, luteolin, and apigenin were 3.1 +/- 0.2/8.2 +/- 0.6, 3.3 +/- 0.3/9.6 +/- 0.5, 3.9 +/- 0.3/10.1 +/- 0.8, 22.9 +/- 1.7/18.2 +/- 0.7, and 338.8 +/- 23.1/ 73.1 +/- 6.4 muM, respectively. The antilipoperoxidative activity of apigenin differed from its cytoprotective effects, but correlated with the free radical scavenging of 2,2-diphenyl-1-picrylhydrazyl radical and half peak oxidation potential (E-p/2). Apigenin was the least effective of the flavonoids studied in all models except the cardiomyocyte model where its cardiomyocyte cytoprotective effect was comparable to other compounds. Copyright (C) 2004 John Wiley Sons, Ltd.