Modified hemoglobin red blood cell substitutes have a number of potential areas of application. In some of these applications, it will be important to lessen the pro-oxidant effects of hemoglobin and potential free radical-mediated toxicity. This research introduces a novel modified hemoglobin that is based on intermolecularly crosslinking hemoglobin, superoxide dismutase and catalase (PolyHb-SOD-CAT) with the bifunctional agent, glutaraldehyde. Superoxide dismutase and catalase catalyze the breakdown of superoxide radical and hydrogen peroxide respectively. Studies of structural and functional parameters reveal that PolyHb-SOD-CAT retains superoxide dismutase and catalase enzymatic activity, and consists of a mixture of molecular species ranging in molecular size and protein composition. Circulation time studies of PolyHb-SOD-CAT in rats show that hemoglobin, superoxide dismutase and catalase possess longer circulatory half-lives as compared to the free forms of these proteins. Studies also show that PolyHb-SOD-CAT prevents the formation of methemoglobin, ferrylhemoglobin, hydroxyl radical, free iron, and lipid peroxidation. Ischemia-reperfusion studies using isolated perfused hindlimbs and intestine of rat show that PolyHb-SOD-CAT reduced the formation of hydroxyl radical compared to PolyHb. Altogether, these results suggest that PolyHb-SOD-CAT is a potentially safer modified hemoglobin oxygen carrier by virtue of its ability to detoxify reactive oxygen species, and reduced propensity to promote and participate in oxidative processes.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.42008 |
| Date | January 1997 |
| Creators | D'Agnillo, Felice. |
| Contributors | Chang, T. M. S. (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Physiology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001558687, proquestno: NQ29915, Theses scanned by UMI/ProQuest. |
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