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Glutaraldehyde-Polymerized Hemoglobin: In Search of Improved Performance as Oxygen Carrier in Hemorrhage Models.
Bioinorganic Chemistry and Applications ( IF 3.8 ) Pub Date : 2020-09-01 , DOI: 10.1155/2020/1096573
Anca D Farcas 1, 2, 3 , Vlad Al Toma 1, 2, 3 , Ioana Roman 1 , Bogdan Sevastre 4 , Florina Scurtu 2 , Radu Silaghi-Dumitrescu 2
Affiliation  

Hemoglobin- (Hb-) based oxygen carriers (HBOC) have for several decades been explored for treatment of hemorrhage. In our previous top-up tests, HBOC with lower in vitro prooxidant reactivity (incorporating a peroxidase or serum albumin to this end) showed a measurable but small improvement of oxidative stress-related parameters. Here, such HBOCs are tested in a hemorrhage set-up; ovine hemoglobin is also tested for the first time in such a setting, based on in vitro data showing its improved performance versus bovine Hb against oxidative and nitrosative stress agents. Indeed, ovine Hb performs better than bovine Hb in terms of survival rates, arterial tension, immunology, and histology. On the other hand, unlike in the top-up models, where the nonheme peroxidase rubrerythrin as well as bovine serum albumin copolymerized with Hb were shown to improve the performance of HBOC, in the present hemorrhage models rubrerythrin fails dramatically as HBOC ingredient (with a distinct immunological reaction), whereas serum albumin appears not feasible if its source is a different species (i.e., bovine serum albumin fares distinctly worse than rat serum albumin, in HBOC transfusions in rats). An effect of the matrix in which the HBOCs are dissolved (PBS versus gelofusine versus plasma) is noted.

中文翻译:

戊二醛聚合的血红蛋白:寻找出血模型中作为氧气载体的改进性能。

数十年来,基于血红蛋白(Hb-)的氧气载体(HBOC)已被研究用于治疗出血。在我们先前的补充测试中,具有较低的体外前氧化剂反应性(为此目的加入过氧化物酶或血清白蛋白)的HBOC显示出可测量但与氧化应激相关的参数有很小的改善。在这种情况下,此类HBOC是在出血装置中测试的;还基于体外在这种情况下首次测试了绵羊血红蛋白数据显示其相对于牛血红蛋白具有更好的抗氧化和亚硝化应激的性能。实际上,就存活率,动脉张力,免疫学和组织学而言,绵羊血红蛋白的性能要优于牛血红蛋白。另一方面,与充血模型不同,非血红素过氧化物酶红血球蛋白以及与Hb共聚的牛血清白蛋白被证明可以改善HBOC的性能,在目前的出血模型中,红血球蛋白作为HBOC成分(具有明显的免疫反应),但如果血清白蛋白的来源不同,则似乎不可行(例如,在大鼠的HBOC输注中,牛血清白蛋白的价格明显比大鼠血清白蛋白差)。注意到其中溶解了HBOC的基质的作用(PBS相对于Gelofusine相对于血浆)。
更新日期:2020-09-01
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