Department of Food and Drug, University of Parma, Parma, Italy.
Department of Medicine and Surgery, University of Parma, Parma, Italy; Biopharmanet-TEC, University of Parma, Parma, Italy.
Free Radic Biol Med. 2018 Aug 20;124:299-310. doi: 10.1016/j.freeradbiomed.2018.06.018. Epub 2018 Jun 18.
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.
血红蛋白基氧载体（HBOCs）是一种用于替代输血的研究性治疗方法，已知会对组织造成氧化损伤。为了研究其氧结合特性与这些有害影响之间的相关性，我们在豚鼠输血模型中研究了两种具有不同氧结合特性（但在化学上完全相同）的聚乙二醇化 HBOC。分析血浆样本中的炎症、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中的蛋白质和脂质，以寻找氧化损伤的标志物。总的来说，与自身输血对照组相比，这两种 HBOC 都会产生更高的氧化应激。特别是，与对照组相比，组织 4-羟壬烯醛加合物、组织丙二醛加合物和血浆 8-氧-2'-脱氧鸟苷的水平明显更高。对于丙二醛加合物，用高亲和力 HBOC 处理的动物的肾脏组织中观察到更高的水平，这表明 HBOC 的氧结合特性与其产生的氧化应激之间存在相关性。此外，我们发现高亲和力 HBOC 比低亲和力 HBOC 产生更大的组织氧合作用，这可能与其诱导的更高氧化应激有关。
