Background/Aims: The antiinflammatory, antimicrobial and anticancer drug auranofin has previously been shown to trigger apoptosis, the suicidal death of nucleated cells. Side effects of the drug include anaemia. At least in theory the anaemia could result from stimulation of suicidal death of erythrocytes or eryptosis, which involves cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Methods: Stimulators of eryptosis include oxidative stress and increase of cytosolic Ca2+-activity ([Ca2+]i). In the present study, phosphatidylserine exposure at the cell surface was estimated from annexin V binding, cell volume from forward scatter, hemolysis from hemoglobin release, reactive oxygen species (ROS) from 2′,7′-dichlorodihydrofluorescein diacetate (DCFDA) fluorescence, and [Ca2+]i from Fluo3-fluorescence. Results: A 24 hours exposure of human erythrocytes to auranofin (≥5 μg/ml) significantly increased the percentage of annexin-V-binding cells (from 2.2 ± 0.5 to 17.4 ± 1.5%), significantly decreased forward scatter and significantly enhanced ROS. At higher concentrations (10 μg/ml) auranofin triggered slight hemolysis (from 2.1 ± 0.2 to 3.2 ± 0.3%). Conclusions: Auranofin stimulates cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect at least partially due to induction of oxidative stress.
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机译：背景/目的：抗炎，抗微生物和抗癌药物金诺芬已被证明可引发细胞凋亡，即有核细胞的自杀死亡。该药物的副作用包括贫血。至少在理论上，贫血可能是由于刺激红细胞自杀性死亡或隐匿性引起的，这涉及细胞收缩和细胞膜的混乱，磷脂酰丝氨酸易位至红细胞表面。方法：加密的刺激物包括氧化应激和胞质Ca 2 + -活性（[Ca 2 + ] i ）的增加。在本研究中，从膜联蛋白V结合，向前散射的细胞体积，血红蛋白释放引起的溶血，2'，7'-二氯二氢荧光素二乙酸酯（DCFDA）荧光产生的活性氧（ROS）和来自Fluo3-荧光的[Ca 2 + ] i 。结果：人红细胞暴露于金诺芬（≥5μg/ ml）24小时会显着增加膜联蛋白-V结合细胞的百分比（从2.2±0.5增至17.4±1.5％），显着降低前向散射并显着增强ROS。在较高浓度（10μg/ ml）时，金诺芬引发轻微溶血（从2.1±0.2到3.2±0.3％）。结论：金诺芬可刺激红细胞膜的细胞收缩和磷脂加扰，其作用至少部分归因于氧化应激的诱导。
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