This investigation evaluated the potential protective role of Zn, through modulation of MT, against the teratogenic effects of isotretinoin (ITR), a dermatological drug which causes oxidative damage, in CD-1 mouse embryos. Significant induction of MT by Zn supplementation was observed in mouse embryos both in vivo and in vitro. On gestational day (GD) 6.5, pregnant mice received a subcutaneous Zn injection of 0 (saline), 20 and 40 mg/kg, resulting in embryonic MT concentrations of 12.5, 54.5 and 93.4 $ mu$g/g protein, respectively, after 48h. Embryos were extracted at GD 8.5 and incubated with 0 (saline) and 15 $ mu$M Zn for 48h. There was a six-fold increase in MT expression in the Zn treatment group, resulting in MT concentration of 688 $ mu$g/g protein. Pre-induction of MT by Zn exposure was found to offer protection against subsequent exposure to ITR in vivo and in vitro. Zn injections of 40 and 20 mg/kg to pregnant mice on GD 8.5 and 9.5, respectively, alleviated fetal damage caused by three intragastric intubations of 100 mg ITR/kg on GD 10.5. Zn pre-treatment significantly increased fetal and placental masses, totally eliminated the incidence of cleft palate and lessened the frequency of post-partum mortality by 74%. Pre-treatment of GD 8.5 embryos with a 24h culture period with 15 $ mu$M Zn improved growth and totally restored normal embryonic development altered by a 24h culture with 17 $ mu$M ITR. Zn decreased the frequencies of unfused mid brain and fore brain by 100%, and the incidence of abnormal flexion by 74%. A reduction in MT concentrations was observed in groups exposed to ITR, indicating that MT may have been oxidized by ITR-derived toxic FR. (Abstract shortened by UMI.)
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.23988 |
| Date | January 1996 |
| Creators | Blain, Danielle. |
| Contributors | Chan, Laurie (advisor), Kubow, Stan (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: 001538791, proquestno: MM19797, Theses scanned by UMI/ProQuest. |
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