Alomari, EAM and Ronda, L and Bruno, S and Paredi, G and Marchetti, M and Bettati, S and Olivari, D and Fumagalli, F and Novelli, D and Ristagno, G and Latini, R and Cooper, CE and Reeder, BJ and Mozzarelli, A (2018) 'High- and low-affinity PEGylated hemoglobin-based oxygen carriers: differential oxidative stress in a Guinea pig transfusion model.' Free Radical Biology and Medicine, 124. 299 - 310. ISSN 0891-5849

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Abstract

Hemoglobin (Hb)-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 PEG-Hboxy, 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.

Item Type:	Article
Uncontrolled Keywords:	Hemoglobin-based oxygen carriers, blood substitutes, oxidative stress, 8-oxo-2'-deoxyguanosine, 4-hydroxynonenal, malondialdehyde, oxygen affinity
Subjects:	Q Science > QH Natural history > QH301 Biology
Depositing User:	Elements
Date Deposited:	09 Aug 2018 15:57
Last Modified:	01 Aug 2019 21:17
URI:	http://repository.essex.ac.uk/id/eprint/22814

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