Horáková Lubica, Licht Anke, Sandig Grit, Jakstadt Manuela, Duracková Zdena, Grune Tilman
Neuroscience Research Center, Medical Faculty (Charité), Humboldt University Berlin, Schumannstr. 20/21, 10098 Berlin, Germany.
Arch Toxicol. 2003 Jan;77(1):22-9. doi: 10.1007/s00204-002-0409-8. Epub 2002 Oct 16.
Oxidative stress plays an important role in cell death associated with many diseases. In the present study, concentration-dependence of hydrogen peroxide on rat pheochromocytoma (PC12) cell viability was studied. Preventive effects of antioxidants on the viability of these cells treated with 2 mM hydrogen peroxide were compared. Trolox and Stobadine, as chain-breaking antioxidants were studied in comparison with standardized extracts of flavonoids of Ginkgo biloba and Pycnogenol, known as agents effective in several diseases. All antioxidants increased the viability of hydrogen peroxide-treated PC12 cells. Flavonoid extracts were more effective than Trolox and Stobadine. Antioxidants were most effective if present after the oxidative treatment. As expected, the preloading with antioxidants was without effect on cell viability. Correlations between viability increase induced by antioxidants, and content of oxidation products of proteins and lipids were studied at concentrations of antioxidants mostly effective in preventing cell death: Trolox (10 microM), Stobadine (30 microM), Ginkgo biloba (160 microg/ml), Pycnogenol (100 microg/ml). In these concentrations, antioxidants did not statistically significantly decrease the content of protein carbonyls, with exception of Stobadine, which had no effect. Ginkgo biloba, Trolox and Stobadine intensively decreased the content of malondialdehyde, a product of lipid peroxidation. Pycnogenol was without any preventive effect. Concentrations of antioxidants with a large effect on viability of PC12 cells were not effective in preventing oxygen radical-induced injury of proteins. Antioxidants prevented the oxidative injury of lipids more effectively than that of proteins.
氧化应激在与多种疾病相关的细胞死亡中起重要作用。在本研究中,研究了过氧化氢浓度对大鼠嗜铬细胞瘤(PC12)细胞活力的依赖性。比较了抗氧化剂对用2 mM过氧化氢处理的这些细胞活力的预防作用。将特洛克斯(Trolox)和司他定(Stobadine)作为链断裂抗氧化剂,与银杏叶和碧萝芷(Pycnogenol)的标准化类黄酮提取物进行比较,后者是在多种疾病中有效的药物。所有抗氧化剂均提高了用过氧化氢处理的PC12细胞的活力。类黄酮提取物比特洛克斯和司他定更有效。如果在氧化处理后存在抗氧化剂,则其效果最佳。正如预期的那样,预先加载抗氧化剂对细胞活力没有影响。在最有效地预防细胞死亡的抗氧化剂浓度下,研究了抗氧化剂诱导的活力增加与蛋白质和脂质氧化产物含量之间的相关性:特洛克斯(10 microM)、司他定(30 microM)、银杏叶(160 microg/ml)、碧萝芷(100 microg/ml)。在这些浓度下,除司他定无作用外,抗氧化剂并未在统计学上显著降低蛋白质羰基的含量。银杏叶、特洛克斯和司他定显著降低了脂质过氧化产物丙二醛的含量。碧萝芷没有任何预防作用。对PC12细胞活力有显著影响的抗氧化剂浓度对预防氧自由基诱导的蛋白质损伤无效。抗氧化剂对脂质氧化损伤的预防比对蛋白质的更有效。