Oral consumption of flaxseed improves serum lipid parameters, and the flaxseed lignan, secoisolariciresinol diglucoside (SDG) may mediate these effects. SDGs therapeutic potential cannot be fully realized until its mechanism of action and pharmacokinetics are more completely characterized.</p>This research aimed to assess SDGs effects in dietary models of hypertriglyceridemia, hypercholesterolemia, and obesity. Furthermore, this thesis work provided preliminary pharmacokinetic data on SDGs aglycone form, secoisolariciresinol (SECO).
Dietary manipulations were used to induce hyperlipidemic states in female Wistar or male Sprague-Dawley rats. Groups of 10 rats were randomly assigned to one of three (obesity and cholesterol diets) or four (fructose) treatment groups: 1) Normal diet with 0.0 µmol SDG/kg body weight; 2) Dietary manipulation with 0.0 µmol SDG/kg; 3) Dietary manipulation with 4.4 µmol SDG/kg; and 4) 10% fructose in water with 8.8 µmol SDG/kg. Lignan or vehicle (saline) was administered daily by oral gavage for four weeks (2 weeks for male Sprague-Dawleys). After four (or two) weeks of SDG administration, body and liver weights were recorded, serum lipids were measured using enzymatic kits, hepatic fat accumulation was determined by histochemical analysis and hepatic mRNA expression of triglyceride pathway targets was evaluated using real-time RT-PCR. A 10% fructose in water model was effective for the induction of hypertriglyceridemia in male Sprague-Dawley rats but ineffective in female Wistar rats of similar age. Neither 4.4 nor 8.8 µmol SDG/kg improved serum and hepatic triglyceride parameters in male Sprague-Dawley rats on a 10% fructose in water diet. It is suspected that gender and strain are important factors for this model of hypertriglyceridemia. Dietary manipulations for the induction of hypercholesterolemia and obesity in female Wistar rats were not effective following 4 weeks administration of a 1% cholesterol diet and a 45% fat diet respectively. Since previous studies were able to successfully induce hypercholesterolemia in the same model, it is suspected that the differences in age of the animals accounted for the inconsistent results. Strain, gender and age of animals were identified as important considerations when trying to induce hyperlipidemic states through dietary manipulations.</p>SDG (4.4 µmol/kg) dosed daily for four weeks caused no gross morphological organ changes or alterations in blood chemistry or hematology parameters. Following an intravenous bolus (10 mg/kg), secoisolariciresinol (SECO) disposition was consistent with two-compartment pharmacokinetics, with distribution and elimination half-lives at 26 seconds and 5 minutes, respectively. No SECO was detected in the plasma following an oral bolus (10 mg/kg).
Further investigation into SDGs hypolipidemic effects are required to elucidate its mechanism of action. A complete pharmacokinetic study is warranted to fully understand SDGs safety and efficacy.
| Identifer | oai:union.ndltd.org:USASK/oai:usask.ca:etd-01232006-123919 |
| Date | 23 January 2006 |
| Creators | Woo, Gloria |
| Contributors | Suveges, Linda, Muir, Alister D., Krol, Ed S., Bandy, Brian, Alcorn, Jane |
| Publisher | University of Saskatchewan |
| Source Sets | University of Saskatchewan Library |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://library.usask.ca/theses/available/etd-01232006-123919/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Saskatchewan or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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