Porcine hepatocyte apoptosis and reduction of albumin secretion induced by deoxynivalenol
Porcine hepatocyte apoptosis and reduction of albumin secretion induced by deoxynivalenol
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DOI：
10.1016/j.tox.2004.07.001
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发表时间：
2004-11-15
期刊：
影响因子：
4.5
通讯作者：
Nakajima, Y
中科院分区：
文献类型：
--
作者：
Mikami, O;Yamamoto, S;Nakajima, Y
脱氧雪腐镰刀菌烯醇（DON）是谷物中主要的真菌毒性污染物之一，可导致猪体重增加减少。本实验研究了DON对猪肝细胞的细胞毒性作用。将终浓度为100、10、1、0.1或0.01 μ g/ml的DON加入到原代培养肝细胞的培养基中。在DON 100和10 μ g/ml组中，从加入后6小时开始观察到肝细胞死亡，在DON 100、10、1和0.1 μ g/ml组中，在24小时以剂量依赖性方式观察到肝细胞死亡。死亡的肝细胞显示染色质浓缩和细胞核碎裂，这被认为是细胞凋亡的特征性形态学变化。TUNEL法显示死亡肝细胞核染色阳性。乳酸脱氢酶（LDH）的释放，这被认为是从凋亡肝细胞泄漏到培养基中，是明显的DON添加后24小时。在DON 100、10和1 μ g/ml组中观察到caspase-3活性增加。在DON 100、10和1 μ g/ml组中，分泌到培养基中的白蛋白显著减少，在0.1 μ g/ml组中中度减少，在0.01 μ g/ml组中轻微减少。这些结果表明，DON通过caspase-3激活途径诱导猪肝细胞凋亡，并导致功能障碍。(C)2004爱思唯尔爱尔兰有限公司保留所有权利。
Deoxynivalenol (DON) is one of the major mycotoxic contaminants of grains, which causes reduced weight gain in pigs. The cytotoxicity of DON to porcine hepatocytes was examined in this study. DON was added at the final concentration of 100, 10, 1, 0.1 or 0.01 mug/ml to the medium of primary cultured hepatocytes. Cell death of the hepatocytes was observed in DON 100 and 10 mug/ml groups from 6 h after the addition, and in DON 100, 10, 1 and 0.1 mug/ml groups at 24 h in a dose-dependent manner. The dead hepatocytes showed chromatin condensation and fragmentation of the nuclei, which are considered characteristic morphological changes of apoptosis. The nuclei of the dead hepatocytes were stained positively by the TUNEL method. Lactate dehydrogenase (LDH) release, which is considered leakage from apoptotic hepatocytes into the medium, was apparent at 24 h after DON addition. Increased caspase-3 activity was seen in DON 100, 10 and 1 mug/ml groups. Albumin secretion into the medium was significantly reduced in DON 100, 10 and 1 mug/ml groups, moderately in the 0.1 mug/ml group, and slightly in the 0.01 mug/ml group. These results indicate that DON induced apoptosis through the caspase-3 activation pathway and caused functional disorder in porcine hepatocytes. (C) 2004 Elsevier Ireland Ltd. All rights reserved.