Pyrrolizidine alkaloid clivorine-induced oxidative stress injury in human normal liver L-02 cells.

Pyrrolizidine alkaloid clivorine-induced oxidative stress injury in human normal liver L-02 cells.
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发表时间:
2009-12
影响因子:
3.1
通讯作者:
Qingning Liang;Tianyu Liu;Lili Ji;Yang Min;Yuye Xia
Qingning Liang;Tianyu Liu;Lili Ji;Yang Min;Yuye Xia
中科院分区:
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文献类型:
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作者:
Qingning Liang;Tianyu Liu;Lili Ji;Yang Min;Yuye Xia

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克氏草碱是从中草药厚朴中分离得到的一种内酯碱型吡咯里西定生物碱。吡咯里西丁生物碱(PAS)是一种广泛分布于世界各地的著名肝毒素。本研究旨在评价克利夫林对人正常肝L-02细胞的氧化损伤作用。用不同浓度的克利伏林处理细胞48h后,测定细胞总抗氧化能力、谷胱甘肽S转移酶(GST)和谷胱甘肽还原酶(GR)来评价氧化损伤程度。结果表明,在克利福林作用下,L-02细胞的总抗氧化能力和谷胱甘肽转移酶活性均升高,而克利福林则降低细胞内GR活性。此外,还观察了抗坏血酸(Vc)、曲洛克斯、二硫苏糖醇(DTT)和甘露醇等抗氧化剂对CLOVOVINE诱导的细胞毒性的保护作用。结果表明,生育酚(维生素E,Ve)的类似物曲洛克斯能拮抗克利伏林对L-02细胞的细胞毒作用。综上所述,这些结果揭示了克利夫林对人肝L-02细胞的氧化损伤作用。这些结果还表明,曲洛克斯可能用于减少克利伏林所致的肝毒性。
Clivorine is an otonecine-type pyrrolizidine alkaloid isolated from the traditional Chinese medicine Ligularia hodgsonii Hook. Pyrrolizidine alkaloids (PAs) are well-known hepatotoxins widely distributed around the world. The present study sought to evaluate clivorineinduced oxidative injury in human normal liver L-02 cells. After cells were treated with various concentrations of clivorine for 48 h, cellular total antioxidant capacity, glutathione-S-transferase (GST) and glutathione reductase (GR) were determined to evaluate oxidative injury. Results showed that cellular total antioxidant capacity and GST activity both increased in clivorine-treated L-02 cells, while clivorine decreased GR activity in cells. Further, the protective effects of some antioxidants such as ascorbic acid (vitamin C, Vc), Trolox, dithiothreitol (DTT) and mannitol against clivorine-induced cytotoxicity were observed. Results showed that Trolox, which is an analogue of tocopherol (vitamin E, Ve), prevented clivorine-induced cytotoxicity in L-02 cells. Taken together, these results revealed clivorineinduced oxidative injury in human liver L-02 cells. These results also indicated the possible use of Trolox in the reduction of clivorine-induced hepatotoxicity.