Acetaminophen-induced cytotoxicity on human normal liver L-02 cells and the protection of antioxidants
Acetaminophen-induced cytotoxicity on human normal liver L-02 cells and the protection of antioxidants
复制标题
对乙酰氨基酚对人正常肝 L-02 细胞的细胞毒性及抗氧化剂的保护
DOI：
10.3109/15376516.2010.482963
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发表时间：
2010-05
影响因子：
3.2
通讯作者：
Wang Zhengtao
中科院分区：
文献类型：
--
作者：
Sheng Yuchen;Ji Lili;Min Yang;Liang Qingning;Xia Yuye;Wang Zhengtao
体外细胞模型可以部分模拟体内反应，为毒理学评估提供了潜在的敏感工具。本研究的目的是探讨对乙酰氨基酚（AP）对人正常肝细胞L-02细胞毒性的可能机制。据报道，将AP转化为其毒性代谢产物的CYP 2 E1酶的表达在L-02细胞中高于Hep 3B细胞。进一步的细胞活力和还原型谷胱甘肽（GSH）消耗后AP处理进行了检查。暴露于AP 24 h后，细胞活力以浓度依赖性方式下降。AP处理48 h后，还观察到浓度依赖性GSH耗竭，表明L-02细胞中发生了氧化应激。同时研究了GSH合成抑制剂D，L-丁硫基-（S，R）-亚砜亚胺（BSO）和GSH合成前体N-乙酰半胱氨酸（NAC）对AP细胞毒作用的影响。BSO可加重AP诱导的细胞毒性，而NAC可减轻AP诱导的细胞死亡。进一步的结果显示，10 mM AP处理48 h后，基于DNA片段化分析和caspase-3激活的蛋白质印迹法，分别引起细胞凋亡。此外，还观察了各种已知的抗氧化剂对AP诱导的肝毒性的保护作用。这些结果表明，氧化应激和细胞凋亡参与了AP诱导的人正常肝L-02细胞毒性，该细胞系是AP肝毒性研究的合适体外细胞模型。
In vitro cell models, which can partially mimic in vivo responses, offer potentially sensitive tools for toxicological assessment. The objective of this study was to explore the possible mechanisms of acetaminophen (AP)-induced toxicity in human normal liver L-02 cells. The expression of the CYP2E1 enzyme, which is reported to transform AP to its toxic metabolites, was higher in L-02 than in Hep3B cells. Further cell viability and reduced glutathione (GSH) depletion after AP treatment were examined. After exposure to AP for 24 h, cell viability decreased in a concentration-dependent manner. Concentration-dependent GSH depletion was also observed after AP treatment for 48 h, indicating oxidative stress had occurred in L-02 cells. The effects of D, L-buthionine-(S, R)-sulfoximine (BSO), an inhibitor of GSH biosynthesis, and N-acetylcysteine (NAC), a precursor of GSH synthesis, on the cytotoxicity induced by AP were also investigated. BSO aggravated the cytotoxicity induced by AP while NAC ameliorated such cell death. Further results showed that 10 mM AP caused cell apoptosis after 48 h treatment based on the DNA fragmentation assay and western blot of caspase-3 activation, respectively. In addition, the protective effects of various well-known antioxidants against AP-induced hepatotoxicity were observed. Taken together, these results indicate that oxidative stress and cellular apoptosis are involved in AP-induced toxicity in human normal liver L-02 cells, and this cell line is a suitable in vitro cell model for AP hepatotoxicity study.
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影响因子：
2.9
作者：
J. Beckers;P. Boček
通讯作者：
J. Beckers;P. Boček
影响因子：
5.9
作者：
Pumford, NR;Halmes, NC;Hinson, JA
通讯作者：
Hinson, JA
影响因子：
--
作者：
Manov, I;Hirsh, M;Iancu, TC
通讯作者：
Iancu, TC
影响因子：
4.5
作者：
Abdel-Zaher, Ahmed O.;Abdel-Hady, Randa H.;Farrag, Magda M. Y.
通讯作者：
Farrag, Magda M. Y.
DOI：
10.1007/s001090050137
发表时间：
1997-07
期刊：
Journal of Molecular Medicine
影响因子：
--
作者：
A. Hołownia;J. Mapoles;J. Menez;J. Braszko
通讯作者：
A. Hołownia;J. Mapoles;J. Menez;J. Braszko