Mitochondrial toxicity of triclosan on mammalian cells.
Mitochondrial toxicity of triclosan on mammalian cells.
复制标题
DOI：
10.1016/j.toxrep.2015.03.012
复制
发表时间：
2015
影响因子：
--
通讯作者：
Salkinoja-Salonen M
中科院分区：
文献类型：
--
作者：
Ajao C;Andersson MA;Teplova VV;Nagy S;Gahmberg CG;Andersson LC;Hautaniemi M;Kakasi B;Roivainen M;Salkinoja-Salonen M
我们展示了三氯生(TCS)对六种哺乳动物细胞的(亚)细胞毒性。1-5μg/ml−-1TCS可引起代谢性酸化和非偶联呼吸。TCS在1μg/mlATP1时停止了猪精子的运动。TCS解偶联线粒体−合成酶复合体V。TCS可使胰岛退变为固缩细胞。以人外周血单核细胞(PBMC)、角质形成细胞(HaCaT)、猪精子和肾小管上皮细胞(PK-15)、小鼠胰岛(Min-6)和神经母细胞瘤细胞(MNA)为靶细胞，研究了三氯生(5-氯-2‘-(2，4-二氯苯氧基)苯酚)对哺乳动物细胞的作用。我们发现，三氯生(1-10μg/ml−1)可使线粒体去极化，使外周血红细胞、HACaT、PK-15和MNA的葡萄糖消耗速率上移，从而导致代谢性酸中毒。三氯生导致产生胰岛素的胰岛退化为微小固缩细胞和坏死性死亡。短期暴露于低浓度三氯生(30min，≤1和μg/ml)可使精子的高幅度尾部拍打和前进运动瘫痪，在30min内使精子线粒体去极化，精子头部顶体区域和鞭毛纤维鞘(鞭毛的远端部分)超极化。用分离的大鼠肝线粒体进行的实验表明，三氯生损害氧化磷酸化，使ATP合成下移，解偶联呼吸，并引起过度摄氧量。这些暴露浓度比消费品中允许的浓度低100-1000倍。三氯生的线粒体毒性机制不同于呋喃霉素、谷氨酰胺和冬凌草素，其作用机制不涉及钾离子通道活性。
We show (sub)cellular toxicity of triclosan (TCS) on six types of mammalian cells. 1–5 μg ml−1 TCS induced metabolic acidification and uncoupled respiration. TCS ceased progressive boar sperm motility at 1 μg ml−1. TCS uncouples ATP synthetase complex V in mitochondrion. TCS caused regression of pancreatic islets to pycnotic cells. Effects of triclosan (5-chloro-2′-(2,4-dichlorophenoxy)phenol) on mammalian cells were investigated using human peripheral blood mono nuclear cells (PBMC), keratinocytes (HaCaT), porcine spermatozoa and kidney tubular epithelial cells (PK-15), murine pancreatic islets (MIN-6) and neuroblastoma cells (MNA) as targets. We show that triclosan (1–10 μg ml−1) depolarised the mitochondria, upshifted the rate of glucose consumption in PMBC, HaCaT, PK-15 and MNA, and subsequently induced metabolic acidosis. Triclosan induced a regression of insulin producing pancreatic islets into tiny pycnotic cells and necrotic death. Short exposure to low concentrations of triclosan (30 min, ≤1 μg/ml) paralyzed the high amplitude tail beating and progressive motility of spermatozoa, within 30 min exposure, depolarized the spermatozoan mitochondria and hyperpolarised the acrosome region of the sperm head and the flagellar fibrous sheath (distal part of the flagellum). Experiments with isolated rat liver mitochondria showed that triclosan impaired oxidative phosphorylation, downshifted ATP synthesis, uncoupled respiration and provoked excessive oxygen uptake. These exposure concentrations are 100–1000 fold lower that those permitted in consumer goods. The mitochondriotoxic mechanism of triclosan differs from that of valinomycin, cereulide and the enniatins by not involving potassium ionophoric activity.