Yi Xiaoyang, Liu Minxia, Luo Qun, Zhuo Hailong, Cao Hui, Wang Jiexi, Han Ying
Beijing Institute of Transfusion Medicine Beijing China.
Department of Transfusion Affiliated Hospital of Academy of Military Medical Sciences Beijing China.
FEBS Open Bio. 2017 Feb 20;7(4):485-494. doi: 10.1002/2211-5463.12193. eCollection 2017 Apr.
Dimethyl sulfoxide (DMSO) is widely used in biological studies as a cryoprotective agent for cells and tissues, and also for cryopreserved platelets (PLTs). However, few data on the toxic effects of DMSO following intravenous infusion of cryopreserved PLTs are available. The aim of this study was to explore dose-related effects of DMSO on red blood cells (RBCs), PLTs and vascular endothelial cells . The results showed that DMSO treatments had significant effects on RBCs, affecting osmotic fragility and increasing hemolysis. Free hemoglobin (FHb) level of RBCs was 0.64 ± 0.19 g L after incubation for 6 h with 0.6% DMSO, and these levels were elevated compared with controls (0.09 ± 0.05 g L). Aggregation of PLTs induced by adenosine diphosphate, thrombin (THR), and thrombin receptor activator peptide (TRAP) were inhibited by DMSO treatment because the THR generation capacity was reduced. The intensity of the cytosolic esterase-induced fluorescence response from carboxy dimethyl fluorescein diacetate (CMFDA) in PLTs was decreased about 29% ± 0.04% after treatment with DMSO. DMSO also inhibited the proliferation of the vascular endothelial cell line EAhy926 cells by blocking the G1 phase. Apoptosis of EAhy926 cells with 0.6% DMSO stimulation was increased threefold compared to controls. On the basis of these findings, it was concluded that DMSO was toxic to the hematologic system. This should be taken into account when assessing the infusion effects of cryopreserved PLTs or other blood products requiring DMSO as a vehicle, such as cryopreserved stem cells, in order to avoid adverse therapeutic effects.
二甲基亚砜(DMSO)在生物学研究中被广泛用作细胞和组织的冷冻保护剂,也用于冷冻保存的血小板(PLT)。然而,关于静脉输注冷冻保存的PLT后DMSO的毒性作用的数据很少。本研究的目的是探讨DMSO对红细胞(RBC)、PLT和血管内皮细胞的剂量相关影响。结果表明,DMSO处理对RBC有显著影响,影响渗透脆性并增加溶血。在0.6%DMSO孵育6小时后,RBC的游离血红蛋白(FHb)水平为0.64±0.19 g/L,与对照组(0.09±0.05 g/L)相比,这些水平升高。DMSO处理抑制了二磷酸腺苷、凝血酶(THR)和凝血酶受体激活肽(TRAP)诱导的PLT聚集,因为THR生成能力降低。用DMSO处理后,PLT中羧基二甲基荧光素二乙酸酯(CMFDA)的胞质酯酶诱导荧光反应强度降低了约29%±0.04%。DMSO还通过阻断G1期抑制血管内皮细胞系EAhy926细胞的增殖。与对照组相比,0.6%DMSO刺激的EAhy926细胞凋亡增加了三倍。基于这些发现,得出结论:DMSO对血液系统有毒性。在评估冷冻保存的PLT或其他需要DMSO作为载体的血液制品(如冷冻保存的干细胞)的输注效果时,应考虑到这一点,以避免不良治疗效果。