High- and low-affinity PEGylated hemoglobin-based oxygen carriers: Differential oxidative stress in a Guinea pig transfusion model.
High- and low-affinity PEGylated hemoglobin-based oxygen carriers: Differential oxidative stress in a Guinea pig transfusion model.
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DOI：
10.1016/j.freeradbiomed.2018.06.018
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发表时间：
2018-08-20
影响因子：
7.4
通讯作者：
Mozzarelli A
中科院分区：
文献类型：
--
作者：
Alomari E;Ronda L;Bruno S;Paredi G;Marchetti M;Bettati S;Olivari D;Fumagalli F;Novelli D;Ristagno G;Latini R;Cooper CE;Reeder BJ;Mozzarelli A
基于血红蛋白的氧载体（HBOCs）是输血的研究替代品，已知会对组织造成氧化损伤。为了研究它们的氧结合特性与这些有害作用之间的相关性，我们在豚鼠输血模型中研究了两种具有不同氧结合特性但在其他方面化学性质相同的PEG化HBOC。分析血浆样品的炎症、组织损伤和器官功能障碍的生化标志物;分析心脏和肾脏提取物的蛋白质和脂质的氧化损伤标志物。总体而言，与自体输血对照组相比，两种HBOC产生更高的氧化应激。特别是，与对照组相比，组织4-羟基壬烯醛加合物、组织丙二醛加合物和血浆8-氧代-2 '-脱氧鸟苷表现出显著更高的水平。对于丙二醛加合物，在用高亲和力HBOC处理的动物的肾组织中观察到更高的水平，暗示HBOC氧结合特性与它们产生的氧化应激之间的相关性。此外，我们发现，高亲和力的HBOC产生更大的组织氧合相比，低亲和力的，可能与较高的氧化应激诱导。两种基于血红蛋白的氧载体在输血模型中导致氧化应激。这两种产品都导致心脏损伤和肾功能障碍的标志物增加。对模型的氧化应激的组织和血浆标志物进行了验证。最高亲和力的氧载体诱导更高的氧化应激。
Hemoglobin-based oxygen carriers (HBOCs) are an investigational replacement for blood transfusions and are known to cause oxidative damage to tissues. To investigate the correlation between their oxygen binding properties and these detrimental effects, we investigated two PEGylated HBOCs endowed with different oxygen binding properties - but otherwise chemically identical - in a Guinea pig transfusion model. Plasma samples were analyzed for biochemical markers of inflammation, tissue damage and organ dysfunction; proteins and lipids of heart and kidney extracts were analyzed for markers of oxidative damage. Overall, both HBOCs produced higher oxidative stress in comparison to an auto-transfusion control group. Particularly, tissue 4-hydroxynonenal adducts, tissue malondialdehyde adducts and plasma 8-oxo-2'-deoxyguanosine exhibited significantly higher levels in comparison with the control group. For malondialdehyde adducts, a higher level in the renal tissue was observed for animals treated with the high-affinity HBOC, hinting at a correlation between the HBOCs oxygen binding properties and the oxidative stress they produce. Moreover, we found that the high-affinity HBOC produced greater tissue oxygenation in comparison with the low affinity one, possibly correlating with the higher oxidative stress it induced. Two hemoglobin-based oxygen carriers led to oxidative stress in a transfusion model. Both products caused an increase in markers of heart damage and kidney dysfunction. Tissue and plasma markers of oxidative stress were validated for the model. The highest-affinity oxygen carrier induced higher oxidative stress.
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影响因子：
4.7
作者：
Caccia, Dario;Ronda, Luca;Mozzarelli, Andrea
通讯作者：
Mozzarelli, Andrea
影响因子：
3.1
作者：
Cole, Russell;Vandegriff, Kim;Winslow, Robert
通讯作者：
Winslow, Robert
影响因子：
6
作者：
Levy, JH;Goodnough, LT;Vlahakes, GJ
通讯作者：
Vlahakes, GJ
影响因子：
4.7
作者：
Manjula, BN;Tsai, S;Acharya, AS
通讯作者：
Acharya, AS
DOI：
10.3109/10731199809119778
发表时间：
1998-01-01
影响因子：
--
作者：
Conover, C;Linberg, R;Shorr, RGL
通讯作者：
Shorr, RGL