Peer-Reviewed Journal Details
Mandatory Fields
H.F. Schött, C. Husche, S. Friedrichs, C.M. Miller, F.O. McCarthy, U. Laufs, J. Plat, O. Weingärtner, D. Lütjohann
7β-Hydroxysitosterol crosses the blood-brain barrier more favored than its substrate sitosterol in ApoE -/-mice
Scopus: 4 ()
Optional Fields
ApoE -/- mice; plant sterols; sitosterol; brain oxyphytosterols; oxysterols; phytosterols
Part B
In this study, we compare the distribution of intraperitoneally injected sitosterol, 7β-hydroxysitosterol or vehicle only (control) for 28 days in male ApoE -/- mice. Furthermore we examine its impact on surrogate markers of cholesterol biosynthesis and sterol absorption rate in plasma, brain and liver tissues from these animals. Injection of sitosterol revealed a 32.1% (P = 0.013) lower plasma total cholesterol compared with control. Cholesterol corrected plasma and absolute brain and liver levels of sitosterol are 4.1-, 1.7-, and 7.2-fold (P < 0.001 for all) higher, respectively. This is in accordance with a reduced plasma campesterol to cholesterol ratio (-16.2%; P = 0.018) together with a 24.1% (P = 0.047) lower concentration of hepatic lathosterol. After injection of 7β-hydroxysitosterol the concentrations of 7β-hydroxysitosterol in plasma, brain and liver are 21.0-, 65.8- and 42.7-fold (P < 0.001 for all) higher, respectively, compared with control. Injection of 7β-hydroxysitosterol revealed significantly lower plasma cholesterol corrected cholestanol and campesterol (-44.2%; P = 0.001 and -24.5; P = 0.004) as well as lower absolute liver cholestanol levels (-31.9%; P < 0.001) compared with control. Intraperitoneally injected sitosterol and 7β-hydroxysitosterol differently influence cholesterol metabolism in plasma and liver. We conclude that the polar 7β-hydroxysitosterol compound can pass the blood brain barrier with higher efficacy than its substrate, sitosterol. Though present in higher amounts in the brain, both, sitosterol and 7β-hydroxysitosterol do not influence cholesterol metabolism in the brain as proven by our surrogate markers.
Grant Details