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Histologic,
Hematologic, and Biochemical Characteristics of Apo E-Deficient Mice: Effects
of Dietary Cholesterol and Phytosterols
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Mohammed H.
Moghadasian, Lien B. Nguyen, Sarah Shefer, Bruce M. McManus, and Jiri J.
Frohlich |
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Healthy
Heart Program (MHM, JJF) and Cardiovascular Research Laboratory (BMM), Department
of Pathology and Laboratory Medicine, St. PaulHospital and University of
British Columbia, Vancouver, BC, Canada; and Department of Medicine (LBN,
SS), University of Medicine and Dentistry of New Jersey, Newark, New Jersey |
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In this study, we examined
the effects of a "Western-type" diet containing 9% (w/w) fat and
0.15% (w/w) cholesterol, in the presence or absence of 2% (w/w) phytosterol
mixture over an 18-week period in apolipoprotein E-deficient mice. Addition
of phytosterols to the high cholesterol diet was associated with normalization
of the depressed hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase
activity (from 22.3 +/- 6.3 to 55.4 +/- 19.9 pmol/mg protein/minutes, p
< 0.05). This finding was associated with a significant decrease
in plasma and hepatic cholesterol concentrations compared with animals fed
the high cholesterol diet without phytosterols (33.3 +/- 5.0 versus 19.2
+/- 6.2 pmol/mg protein, p < 0.05). The activities of cholesterol
7[alpha]-hydroxylase and sterol 27-hydroxylase were comparable between the
two groups of mice. Urinalyses and hematologic data were comparable between
the two groups except for significantly lower platelet counts in the phytosterol-treated
animals (681.6 +/-118.9 versus 857.1 +/-185.4 9/L, p < 0.05).
The phytosterol-treated animals had significantly (p < 0.05) less
fragile erythrocytes when exposed to 0.08, 0.07, or 0.05 M
NaCl compared with cholesterol-fed mice. The consumption of the Western-type
diet was associated with the development of xanthomatous skin lesions in
33% of the cholesterol-fed animals, but in none of the phytosterol-treated
animals. Histologic examination revealed oil red O-negative vacuolation
in liver and kidney parenchymal cells of the cholesterol-fed group, but
not in the phytosterol-treated mice. Arrested spermatogenesis and atrophy
of seminiferous tubules were observed, to a variable extent, in both groups
of animals. We conclude that addition of the phytosterol mixture (2% w/w)
to a Western-type diet in apolipoprotein Emice significantly decreases plasma
and hepatic cholesterol concentrations, increses hepatic 3-hydroxy-3-methylglutaryl-coenzyme
A reductase activity, and prevents cutaneous xanthomatosis and vacuolation
in the parenchymal cells of kidneys and livers. (Lab Invest 1999,
79:355-364). |
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