High- and low-affinity PEGylated hemoglobin-based oxygen carriers: Differential oxidative stress in a Guinea pig transfusion model

Autor: Francesca Fumagalli, Giuseppe Ristagno, Luca Ronda, Esra'a Alomari, Davide Olivari, Gianluca Paredi, Roberto Latini, Chris E. Cooper, Stefano Bettati, Marialaura Marchetti, Deborah Novelli, Andrea Mozzarelli, Brandon J. Reeder, Stefano Bruno
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
030204 cardiovascular system & hematology
Pharmacology
medicine.disease_cause
Biochemistry
hs-cTnT
high sensitivity troponin T
chemistry.chemical_compound
0302 clinical medicine
Malondialdehyde
Deoxyguanosine
IHP
inositol hexaphosphate
8-OHdG
8-hydroxy-2'-deoxyguanosine
IMT
2-imino thiolane
Kidney
HNE
4-hydroxynonenale
LDH
lactate dehydrogenase
MAL-PEG
maleimido polyethylene glycol
Hemoglobin-based oxygen carriers
Hct
arterial hematocrit
Oxygen affinity
medicine.anatomical_structure
Models
Animal
LPS
lipopolysaccharide
LAL
Limulus amebocyte lysate
GPT
glutamate-pyruvate transaminase
Guinea Pigs
8-Oxo-2'-deoxyguanosine
HBOC
hemoglobin-based oxygen carrier
GOT
glutamic oxaloacetic transaminase
TCA
trichloroacetic acid
Article
EDTA
ethylenediamine tetraacetic acid
4-Hydroxynonenal
03 medical and health sciences
PBS
phosphate buffered saline
Blood Substitutes
Physiology (medical)
LHP
lipid hydroperoxyde
medicine
Animals
Humans
Blood substitutes
Oxidative stress
8-oxo-2 '-deoxyguanosine
4-hydroxynonenal
PEG
polyethylene glycol
8-oxo-2'-deoxyguanosine
EU
endotoxin unit
HbA
purified human hemoglobin A
DNPH
2
4-dinitrophenylhydrazine
Oxidative Stress
030104 developmental biology
chemistry
BSA
bovine serum albumin
Hemoglobin
Oxygen binding
Zdroj: Free Radical Biology & Medicine
Free radical biology & medicine 124 (2018): 299–310. doi:10.1016/j.freeradbiomed.2018.06.018
info:cnr-pdr/source/autori:Alomari E, Ronda L, Bruno S, Paredi G, Marchetti ML, Bettati S, Olivari D, Fumagalli F, Novelli D, Ristagno G, Latini R, Cooper CE, Reeder BJ, Mozzarelli A/titolo:High-and low-affinity PEGylated hemoglobin-based oxygen carriers: Differential oxidative stress in a Guinea pig transfusion model/doi:10.1016%2Fj.freeradbiomed.2018.06.018/rivista:Free radical biology & medicine/anno:2018/pagina_da:299/pagina_a:310/intervallo_pagine:299–310/volume:124
ISSN: 1873-4596
0891-5849
DOI: 10.1016/j.freeradbiomed.2018.06.018
Popis: 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.
Graphical abstract fx1
Highlights • 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.
Databáze: OpenAIRE
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