Immunotoxicological effects of streptozotocin and alloxan: In vitro and in vivo studies
Immunotoxicological effects of streptozotocin and alloxan: In vitro and in vivo studies
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DOI：
10.1016/j.imlet.2014.12.006
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发表时间：
2015-02-01
影响因子：
4.4
通讯作者：
Hassan, Moustapha
中科院分区：
文献类型：
--
作者：
Diab, Randa A. Hadi;Fares, Mona;Hassan, Moustapha
链脲佐菌素（STZ）和四氧嘧啶（ALX），广泛用于诱导实验动物糖尿病，具有不同的结构和作用机制。我们研究了这些药物对免疫系统的影响，这些影响可能会影响移植模型中的植入效率和移植物存活率，以及它们对造血细胞系的细胞毒性。我们使用最小剂量在小鼠中诱导糖尿病，即180 mg/kg静脉注射STZ和75 mg/kg静脉注射ALX。与对照组相比，两组在给药后4天内体重均显著降低。我们发现，ALX注射小鼠的血糖增加速度比STZ注射小鼠快。回收的脾细胞总数在STZ注射的动物中比在ALX注射的动物中低。与ALX注射受体（6-7天）相比，STZ注射受体（7-24天）的大鼠胰岛移植物在受体小鼠中的存活期更长且更多样化。体外研究表明，ALX对HL 60、K562和C1498细胞的IC 50值分别为2809、3679和>4000 μ g/ml。STZ对HL 60、K562和C1498细胞的IC_（50）分别为11.7、904和1024 μ g/ml。此外，在对刀豆球蛋白A（Con-A）的反应中，STZ注射小鼠的脾细胞产生的干扰素-γ（IFN-γ）的量高于ALX注射小鼠的脾细胞。总之，在体外和体内，STZ比ALX具有更大的细胞毒性。STZ引起淋巴细胞减少症，这可能导致STZ治疗的动物比AIX治疗的动物移植物存活时间更长。(C)2015年欧洲免疫学会联合会。Elsevier B. V.出版，保留所有权利。
Streptozotocin (STZ) and alloxan (ALX), widely used to induce diabetes in experimental animals, have different structures and mechanisms of action. We investigated those effects of these drugs on the immune system that might influence engraftment efficiency and graft survival in transplantation models, and their cytotoxicity on hematopoietic cell lines. We used the minimum dose to induce diabetes in a mouse, i.e. 180 mg/kg i.v. STZ and 75 mg/kg i.v. ALX. Both groups exhibited significant decrease in body weight during 4 days post-treatment as compared to controls. We found that blood glucose in ALX-injected mice increased faster than in STZ-injected mice. The total number of recovered splenocytes was lower in STZ-injected animals than in ALX-injected animals. The survival periods of rat islet grafts in recipient mice were longer and more diverse in STZ-injected recipients (7-24 days) compared to ALX-injected recipients (6-7 days). The in vitro study showed that ALX was less cytotoxic in cell lines with IC50 values of 2809, 3679 and >4000 mu g/ml for HL60, K562 and C1498 cells respectively. STZ was more toxic, especially in HL60 cells, with IC50 values of 11.7, 904 and 1024 mu g/ml for HL60, K562 and C1498 cells respectively. Furthermore, in response to concanavalin A (Con-A), splenocytes from STZ-injected mice produced higher amounts of interferon-gamma (IFN-gamma) than those from ALX-injected mice. In conclusion, STZ was more cytotoxic than ALX in vitro and in vivo. STZ caused lymphocytopenia, which may result in longer graft survival in STZ-treated animals than in AIX-treated animals. (C) 2015 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.