Ezetimibe Promotes Brush Border Membrane-to-Lumen Cholesterol Efflux in the Small Intestine
Fig 4
Effect of ezetimibe on cholesterol transit in mice.
A, An illustrated protocol for the 3H-cholesterol distribution assay. B, Upper; 3H-decay per minute (DPM) count distribution 3 h after 3H-cholesterol was given orally to C57BL/6J mice. Bars indicate mean and the standard deviation (n = 5 for vehicle and n = 4 for ezetimibe). Open bars, vehicle; gray bars, ezetimibe (50 μg). The 3H-DPM abundance in each portion was shown as % as given 3H-DPM as 100% (left, black bar). In the vehicle treatment, almost all the tracer infused was recovered; thus, we did not measure the tracer in the cecum and data of the cecum is absent for the vehicle. In the ezetimibe treatment, the given tracer count was not sufficiently recovered. We then measured the cecum and detected approximately 20% of the given tracer in them. B, Lower; the pie charts show summaries of 3H distribution in the small intestine (tissue), intestinal tract (lumen), and absorbed (the sum of the serum and the liver). C, Dose-dependent inhibitory effect of ezetimibe on fractional cholesterol transit into the serum and the liver. The reduction in tracer activity in enterocytes reached a plateau at 5 μg ezetimibe, whereas reductions in the liver and serum were greater than that in enterocytes with 5 μg and 50 μg ezetimibe. Changes in the distribution are shown with vehicle treatment as 100%. The significance of individual differences was evaluated by using Dunnett’s test. * p < 0.05; ** p < 0.01 vs. vehicle. Bars indicate mean ± SEM (n = 6).