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-defici ent mice. Addition of phytosterols to the high cholesterol diet was associa ted 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 p rotein/minutes, p < 0.05). This finding was associated with a significant d ecrease in plasma and hepatic cholesterol concentrations compared with anim als 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 a lpha-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 phytoster ol-treated animals (681.6 +/- 118.9 versus 857.1 +/- 185.4 x 10(9)/L, p < 0 .05). The phytosterol-treated animals had significantly (p < 0.05) less fra gile 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 associat ed with the development of xanthomatous skin lesions in 33% of the choleste rol-led animals, but in none of the phytosterol-treated animals. Histologic examination revealed oil red O-negative vacuolation in liver and kidney pa renchymal cells of the cholesterol-fed group, but not in the phytosterol-tr eated mice. Arrested spermatogenesis and atrophy of seminiferous tubules we re observed, to a variable extent, in both groups of animals. We conclude t hat 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-co enzyme A reductase activity, and prevents cutaneous xanthomatosis and vacuo lation in the parenchymal cells of kidneys and livers.