Disodium ascorbyl phytostanyl phosphate reduces plasma cholesterol concentrations and atherosclerotic lesion formation in apolipoprotein E-deficient mice.
Disodium ascorbyl phytostanyl phosphate (FM-VP4) consists of ascorbic acid covalently bound to phytostanols by a phosphodiester linkage and is derived as the disodium salt. The purpose of this study was to evaluate the lipid-lowering and antiatherosclerotic properties of FM-VP4 following administration to apolipoprotein E (ApoE)-deficient mice. Four-week-old male C57BL/6J mice with a homozygous deletion of the ApoE gene (apolipoprotein E knock-out) were administered 0 (control), 0.1%, 0.5%, 1.0%, and 2.0% (wt/vol) FM-VP4 in their drinking water or 2.0% FM-VP4 (wt/wt) in their diet for 12 consecutive weeks. All animals received a standard mouse chow diet consisting of 9.0% (wt/wt) fat and 0.2% (wt/wt) cholesterol. Plasma cholesterol and triglyceride levels were determined at baseline and at 4-week intervals (4, 8, and 12 weeks) throughout the term of the study. At the end of the study, mice were killed using CO(2) gas, and blood was taken from the heart. The heart and aorta were removed and sections of the aortic roots were stained with oil red O (ORO) and Movat's stain. The lesions found in this area were measured using a computer-assisted image analysis. Consumption of FM-VP4 by either food or drinking water routes was associated with an approximately 75% reduction in total plasma cholesterol levels and a 75% decrease in aortic atherosclerotic lesion area in ApoE-deficient mice over 12 weeks compared to controls. A trend in decreasing plasma triglyceride levels was also observed. Taken together these data suggest that FM-VP4 has both lipid-lowering and antiatherosclerotic properties following 12-week administration to ApoE-deficient mice.
Lukic
Tatjana
T
Forbes Medi-Tech Inc, Vancouver, Canada.
Wasan
Kishor M
KM
Zamfir
Daniela
D
Moghadasian
Mohammed H
MH
Pritchard
P Haydn
PH
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000473:pathology*; D001205:Ascorbic Acid / Q000494:pharmacology; D002784:Cholesterol / Q000097:blood*; D004032:Diet; D004305:Dose-Response Relationship, Drug; D006651:Histocytochemistry; D007091:Image Processing, Computer-Assisted; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010840:Phytosterols / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D001057:Apolipoproteins E; C445524:FM-VP4 compound; D010840:Phytosterols; D014280:Triglycerides; D002784:Cholesterol; D001205:Ascorbic Acid