Abstract | UNLABELLED: METHODS: Relative circulating levels of astaxanthin derived from CDX-085 administration compared to administration of pure astaxanthin was initially evaluated in a canine model. In mouse Study #1, 16 wild-type and 16 LDLR(-/-) mice on 0.5% cholesterol diet supplemented with either 0.0%, 0.08%, 0.2% and 0.4% CDX-085 were used to assess plasma levels and lipoprotein biodistribution measured by FPLC after 4 weeks treatment. In Study #2, 36 male LDLR(-/-) mice were randomized to a 0.5% cholesterol chow diet (CHOW group, n=12) or 0.5% cholesterol chow fortified with 0.08% CDX-085 (n=12) or 0.5% cholesterol chow with 0.4% CDX-085 (n=12) for 12 weeks. In Study #3, 34 male ApoE(-/-) mice were randomized in the same fashion as the Study #2 and fed similar diets for 9 weeks. RESULTS: CDX-085 administration was shown to result in significantly higher levels of circulating astaxanthin (p<0.001 ANOVA) over a 72 h period compared to pure, non-esterified astaxanthin in a single-dose pharmacokinetic study in beagles. In Study #1, plasma astaxanthin levels were 5-9-fold higher in LDLR(-/-) mice compared to wild-type mice. Astaxanthin was highly distributed among all lipoprotein fractions, generally reflecting cholesterol content of lipoproteins. In Study #2, administration of CDX-085 resulted in significantly lower total cholesterol levels (528±68 mg/dL vs. 550±67 mg/dL vs. 602±80 mg/dL, p=0.047) and aortic arch atherosclerosis (9.0±4.2% vs. 9.8±3.5% vs. 13.2±3.6%, p=0.023) in the 0.4% CDX-085 group compared to the 0.08% CDX-085 and CHOW groups, respectively. In ApoE(-/-) mice, a 72% reduction in triglycerides in the 0.4% CDX-085 group and 50% reduction in the 0.08% CDX-085 groups was noted compared to CHOW group (final levels 17±11 mg/dL vs. 30±15 mg/dL vs. 60±32 mg/dL, respectively, p=0.001). CONCLUSION:
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Authors | Sung Kee Ryu, Timothy J King, Kazutoshi Fujioka, Jennifer Pattison, Fredrick J Pashkow, Sotirios Tsimikas |
Journal | Atherosclerosis
(Atherosclerosis)
Vol. 222
Issue 1
Pg. 99-105
(May 2012)
ISSN: 1879-1484 [Electronic] Ireland |
PMID | 22406426
(Publication Type: Journal Article)
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Copyright | Copyright © 2012 Elsevier Ireland Ltd. All rights reserved. |
Chemical References |
- Apolipoproteins E
- CDV-085
- Lipoproteins
- Prodrugs
- Receptors, LDL
- Triglycerides
- Xanthophylls
- astaxanthine
- Cholesterol
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Topics |
- Animals
- Aortic Diseases
(pathology)
- Apolipoproteins E
(deficiency)
- Atherosclerosis
(pathology, physiopathology)
- Cholesterol
(blood)
- Dogs
- Lipoproteins
(blood)
- Male
- Mice
- Mice, Knockout
- Prodrugs
(pharmacology)
- Receptors, LDL
(deficiency)
- Triglycerides
(blood)
- Xanthophylls
(blood, pharmacology)
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