Histologic, hematologic, and biochemical characteristics of apo E-deficient mice: effects of dietary cholesterol and phytosterols.
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 7alpha-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 x10(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 E-deficient mice significantly decreases plasma and hepatic cholesterol concentrations, increases hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity, and prevents cutaneous xanthomatosis and vacuolation in the parenchymal cells of kidneys and livers.
Moghadasian
M H
MH
Department of Pathology and Laboratory Medicine, St. Paul's Hospital and University of British Columbia, Vancouver, Canada.
Nguyen
L B
LB
Shefer
S
S
McManus
B M
BM
Frohlich
J J
JJ
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D001772:Blood Cell Count; D002784:Cholesterol / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D004032:Diet; D004798:Enzymes / Q000378:metabolism; D007668:Kidney / Q000473:pathology; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D009996:Osmotic Fragility; D010840:Phytosterols / Q000008:administration & dosage* / Q000494:pharmacology; D012867:Skin / Q000473:pathology; D013261:Sterols / Q000378:metabolism; D013737:Testis / Q000473:pathology
D001057:Apolipoproteins E; D002791:Cholesterol, Dietary; D004798:Enzymes; D008055:Lipids; D010840:Phytosterols; D013261:Sterols; D002784:Cholesterol