噻吨酮对红细胞的影响。
Effect of thioridazine on erythrocytes.
机构信息
Department of Physiology, Eberhard-Karls-University of Tuebingen, Gmelinstr.5, Tuebingen 72076, Germany.
出版信息
Toxins (Basel). 2013 Oct 23;5(10):1918-31. doi: 10.3390/toxins5101918.
BACKGROUND
Thioridazine, a neuroleptic phenothiazine with antimicrobial efficacy is known to trigger anemia. At least in theory, the anemia could result from stimulation of suicidal erythrocyte death or eryptosis, which is characterized by cell shrinkage and by phospholipid scrambling of the cell membrane with phosphatidylserine exposure at the erythrocyte surface. Triggers of eryptosis include increase of cytosolic Ca²⁺-concentration (Ca²⁺) and activation of p38 kinase. The present study explored, whether thioridazine elicits eryptosis.
METHODS
Ca²⁺ has been estimated from Fluo3-fluorescence, cell volume from forward scatter, phosphatidylserine exposure from annexin-V-binding, and hemolysis from hemoglobin release.
RESULTS
A 48 hours exposure to thioridazine was followed by a significant increase of Ca²⁺ (30 µM), decrease of forward scatter (30 µM), and increase of annexin-V-binding (≥12 µM). Nominal absence of extracellular Ca²⁺ and p38 kinase inhibitor SB203580 (2 µM) significantly blunted but did not abolish annexin-V-binding following thioridazine exposure.
CONCLUSIONS
Thioridazine stimulates eryptosis, an effect in part due to entry of extracellular Ca²⁺ and activation of p38 kinase.
背景
噻吨嗪是一种具有抗菌功效的神经安定吩噻嗪类药物，已知会引发贫血。至少从理论上讲，贫血可能是由于刺激自杀性红细胞死亡或红细胞皱缩引起的，红细胞皱缩的特征是细胞缩小和细胞膜磷脂酰丝氨酸暴露于红细胞表面的磷脂重排。红细胞皱缩的触发因素包括细胞浆钙离子浓度(Ca²⁺)的增加和 p38 激酶的激活。本研究探讨了噻吨嗪是否会引发红细胞皱缩。
方法
通过 Fluo3 荧光法估计Ca²⁺，通过前向散射测量细胞体积，通过 annexin-V 结合测量磷脂酰丝氨酸暴露，通过血红蛋白释放测量溶血。
结果
噻吨嗪暴露 48 小时后，Ca²⁺（30 µM）显著增加，前向散射（30 µM）降低，annexin-V 结合（≥12 µM）增加。在不存在细胞外 Ca²⁺和 p38 激酶抑制剂 SB203580（2 µM）的情况下，噻吨嗪暴露后 annexin-V 结合显著减弱，但并未完全消除。
结论
噻吨嗪刺激红细胞皱缩，这种作用部分归因于细胞外 Ca²⁺的进入和 p38 激酶的激活。
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