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Permanent link (DOI): https://doi.org/10.7939/R30Q1G

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Evaluation of desiccation-induced oxidative injury in human red blood cells Open Access

Descriptions

Other title
Subject/Keyword
reactive oxygen species
red blood cells
hemoglobin oxidation
dessication
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Kanias, Tamir
Supervisor and department
Acker, Jason (Lab Medicine and Pathology)
Examining committee member and department
Department
Medical Science - Laboratory Medicine and Pathology
Specialization

Date accepted
2010-08-31T21:19:50Z
Graduation date
2010-11
Degree
Doctor of Philosophy
Degree level
Doctoral
Abstract
The current practice of red blood cell banking for transfusion medicine relies primarily on a six-week liquid storage. A growing demand for red blood cell (RBC) products has prompted the search for alternative preservation methods including dry storage. Being desiccation sensitive, attempts to recover RBCs from the dry state have failed. This dissertation offers a new mechanistic understanding of desiccation-induced cellular injury that is correlated with the oxidative state of the hemoglobin. The general hypothesis states that RBC desiccation is accompanied with non-physiological oxidation of hemoglobin and, consequently, the release of toxic products capable of compromising cellular recovery through oxidative injury. Data acquired for this dissertation demonstrates that water loss induces a drastic increase in the rate of hemoglobin oxidation, formation of intracellular reactive oxygen species (ROS), and hemolysis. Pharmacological treatments of the hemoglobin’s oxygen binding site reveal that hemoglobin-induced cellular injury is more prominent in RBC samples that are partially dehydrated (about 3.5 to 5.5 g H2O/g dry weight) than in samples that are relatively dry (≤ 2 g H2O/g dry weight). Furthermore, partially dehydrated RBC samples contain higher levels of oxidized lipids than more fully dried samples. This dissertation also examined the role that glucose and glutathione play in enhancing desiccation tolerance of RBCs. Glucose treatment (5 mmol/L) significantly reduced ROS formation and hemolysis levels in partially dehydrated RBC samples (5.8 ± 0.3 g H2O/g dry weight), but not in samples that are relatively dry (2.8 ± 0.5 g H2O/g dry weight). Treating RBCs with DL-buthionine-(S,R)-sulfoximine, a glutathione depleting agent, was correlated with reduced levels of desiccation-induced hemolysis. This study suggests that desiccation-induced oxidative injury in RBCs is water dependent corresponding to earlier stages of water loss, in which cells can retain metabolic activity. Pharmacological treatments at this stage can significantly affect cell recovery as demonstrated with modifying the hemoglobin’s oxygen binding site, glutathione depletion, and glucose supplementation. On the other hand, increased cytoplasmatic viscosity compromises biochemical reactions at lower residual moisture contents, and cellular injury is likely the result of physical and mechanical stress. These differences should be taken into consideration in the design of innovative approaches to RBC preservation.
Language
English
DOI
doi:10.7939/R30Q1G
Rights
License granted by Tamir Kanias (kanias@ualberta.ca) on 2010-08-31T20:50:36Z (GMT): Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of the above terms. The author reserves all other publication and other rights in association with the copyright in the thesis, and except as herein provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
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