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BACKGROUND: Probucol has been shown to prevent cerebral capillary disturbances characterized by blood-to-brain extravasation of plasma derived proteins and neurovascular inflammation in mice maintained on western-styled diets for 12 weeks. However the effect of probucol on capillary integrity in aging models with capillary dysfunction is not known. METHODS: Wild-type C57BL6 mice were randomized to a low-fat (LF); saturated-fat (SFA); or SFA + Probucol diet for up to12 months of intervention. RESULTS: Mice fed the LF diet had substantially greater parenchymal abundance of plasma derived IgG and apo B lipoproteins at 12 months, compared to LF mice at 3 months of intervention. Markers of neurovascular inflammation were also greater at 12 months in LF fed mice compared to LF mice at 3 months. The SFA diet exacerbated the aging induced parenchymal abundance of IgG and of apo B lipoproteins and neurovascular inflammation at 12 months. The SFA effects were associated with increased production of intestinal lipoprotein amyloid-β (Aβ). The co-provision of probucol with the SFA completely abolished heightened inflammation at 12 months. Probucol attenuated SFA-induced capillary permeability but had only a modest inhibitory effect on parenchymal retention of apoB lipoproteins. The improvements in markers of inflammation and capillary integrity because of probucol correlated with enterocytic genesis of chylomicron Aβ. CONCLUSION: In this long-term feeding study, probucol profoundly suppressed dietary SFA induced disturbances in capillary integrity but had a more modest effect on age-associated changes.

Original publication

DOI

10.1186/1476-511X-13-91

Type

Journal article

Journal

Lipids Health Dis

Publication Date

03/06/2014

Volume

13

Keywords

Animals, Apolipoproteins B, Blood-Brain Barrier, Capillaries, Diet, Fat-Restricted, Female, Immunoglobulin G, Inflammation, Mice, Mice, Inbred C57BL, Probucol