Although the risk of malformations in the offspring of diabetic mothers remains the leading cause of perinatal mortality, the pathogenesis has not been elucidated. The hypothesis of this study was that protein glycation and oxygen free radicals play a role in hyperglycemia-induced malformations. CD-1 mouse embryos (0-2 somites) were cultured under hyperglycemic conditions for 48 hours with the exogenous addition of anti-glycating agents and oxygen free radical scavengers. The exogenous addition of aspirin (ASA) and D-lysine reduced significantly the malformations and embryonic glycated protein levels. Salicylate, arachidonic acid (AA), and to a lesser extent, indomethacin also exerted protective effects, but with no effect on glycated protein levels. We hypothesize that ASA, salicylate and indomethacin are protective by exerting free radical scavenging action; and ASA and D-lysine are acting as potent anti-glycating agents. Moreover, we suggest that AA may have inhibited hyperglycemia-induced malformations through the protective action of prostaglandins against free radical damage. Serum media lipid peroxidation (LPO) was reduced in the ASA and indomethacin groups possibly due to either a direct free radical scavenging action and/or the inhibitory effects of these agents on cyclooxygenase activity thereby decreasing the oxygen free radicals produced by this enzyme system. On the other hand, AA was associated with an increased level of LPO in the serum media. As the evidence has shown, the cause of hyperglycemia-induced malformations appears to be multifactorial and no one agent can completely eliminate the problem, although protective action can be exerted at different levels of the glycation-free radical cascade of tissue damage.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.68163 |
| Date | January 1994 |
| Creators | Chan, Ivy |
| Contributors | Kubow, 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 | Master of Science (School of Dietetics and Human Nutrition.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001395965, proquestno: AAIMM94420, Theses scanned by UMI/ProQuest. |
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