Huang Xian-Ju, Wang Da Gui, Ye Li-Chun, Li Jun, Akhtar Muhammad, Saleem Shahzad, Shi Zhao-Hua, Ihsan Awais
College of Pharmacy, South-Central University for Nationalities, Minyuan Road, 708 Wuhan 430074, P.R. China.
Research Center of Wuhan Aimin Pharmaceutical Co. Ltd., Gedian Economic Development Zone, Ezhou 436070, P.R. China.
Toxicol Res (Camb). 2020 Jun 23;9(4):413-424. doi: 10.1093/toxres/tfaa042. eCollection 2020 Jul.
Sodium aescinate (SA) is a vital salt of sodium escin from Rehd seeds. SA injection (SAI) has received great success in treating cerebral edema, venous reflux disease and other inflammatory conditions. Recently, high incidences of immediate hypersensitivity reactions were reported after SA infusion, which raised questions on safety and risk associated with its clinical application. This study was designed to check whether SAI and its four components induce degranulation using RBL-2H3 mast cells. For this purpose, we evaluated different treatment levels of SAI (20, 40, 60, 80 and 100 μg ml) and its four characteristic components, SA-A, SA-B, SA-C and SA-D, at 60 μg ml in different tests including cell viability test, -hexosaminidase and histamine assays, oxidative stress indices, apoptosis analysis and intracellular calcium ions in RBL-2H3 cells. Our results demonstrated that SAI at 80 μg ml and 100 μg ml, and its two components (SA-B and SA-D) at 60 μg ml were responsible for disturbing cell morphology and cell viability, elevated levels of -hexosaminidase, histamine, modulation of oxidative stress indices, induced apoptosis and increase in intracellular calcium ions in RBL-2H3 cells, when compared with the control. Our results demonstrated for the first time that SAI was more likely to induce immediate hypersensitivity reactions attributable to degranulation via oxidative stress caused by SA-B and SA-D components. These results would not only be useful for the safety of end user but also for the industry to improve the quality of SA infusion.
七叶皂苷钠(SA)是从欧洲七叶树种子中提取的七叶皂苷的重要钠盐。七叶皂苷钠注射剂(SAI)在治疗脑水肿、静脉回流疾病和其他炎症性疾病方面取得了巨大成功。最近,有报道称SA输注后立即发生过敏反应的发生率很高,这引发了对其临床应用安全性和风险的质疑。本研究旨在使用RBL-2H3肥大细胞检查SAI及其四种成分是否会诱导脱颗粒。为此,我们在不同测试中评估了不同处理水平的SAI(20、40、60、80和100μg/ml)及其四种特征成分SA-A、SA-B、SA-C和SA-D(60μg/ml),包括细胞活力测试、β-己糖胺酶和组胺测定、氧化应激指标、凋亡分析以及RBL-2H3细胞内的钙离子。我们的结果表明,与对照组相比,80μg/ml和100μg/ml的SAI以及60μg/ml的两种成分(SA-B和SA-D)会干扰细胞形态和细胞活力,提高β-己糖胺酶、组胺水平,调节氧化应激指标,诱导凋亡并增加RBL-2H3细胞内的钙离子。我们的结果首次表明,SAI更有可能通过SA-B和SA-D成分引起的氧化应激诱导脱颗粒,从而引发立即过敏反应。这些结果不仅对终端用户的安全有用,也有助于该行业提高SA输注的质量。