Effect of Grapefruit Juice Intake on Serum Level of the Endogenous CYP3A4 Metabolite 4-Hydroxycholesterolan Interaction Study in Healthy Volunteers
Effect of Grapefruit Juice Intake on Serum Level of the Endogenous CYP3A4 Metabolite 4-Hydroxycholesterolan Interaction Study in Healthy Volunteers
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DOI：
10.1208/s12248-019-0330-1
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发表时间：
2019-07-01
期刊：
影响因子：
4.5
通讯作者：
Molden, Espen
中科院分区：
文献类型：
--
作者：
Gjestad, Caroline;Hole, Kristine;Molden, Espen
4-羟基胆固醇（4OHC）是内源性CYP3A4代谢物。然而，尚不清楚循环4OHC水平是否反映肝脏CYP3A4活性或肝脏和肠道酶活性。本研究的目的是研究葡萄柚汁对健康志愿者血清4OHC水平的影响，葡萄柚汁被认为是一种选择性肠道CYP3A4抑制剂。参与者（n=22）每天喝两次葡萄柚汁，持续3周，然后是2周的洗脱期。在第0、7、21和35天抽取血液样本，测量4OHC和非cyp3a4衍生的氧甾醇24-羟基胆固醇（24OHC）和27-羟基胆固醇（27OHC），以及胆固醇和总胆固醇。从基线到第1,3和5周，胆固醇校正的4OHC水平的中位个体变化（比率）分别为0.94 (P=0.2), 0.98 （P=0.3）和0.97 （P=0.9）。相比之下，同一点24OHC胆固醇校正水平的中位数变化（比值）分别为1.01 （P=0.6）、0.98 （P=0.3）和0.99 (P=0.5)， 27OHC的中位数变化（比值）分别为1.01 （P=0.8）、0.97 （P=0.5）和0.99 （P=0.2）。令人惊讶的是，血清胆固醇浓度在1周后显著降低了约5% (P=0.03)，而胆固醇校正的中位胆固醇水平在整个5周期间显著并持续增加了约15% （P=0.03）
4-Hydroxycholesterol (4OHC) is an endogenous CYP3A4 metabolite. However, it is unclear whether circulating levels of 4OHC may reflect hepatic CYP3A4 activity or both hepatic and intestinal enzyme activity. The aim of this study was to investigate the effect of grapefruit juice, regarded to be a selective intestinal CYP3A4 inhibitor, on serum 4OHC levels in healthy volunteers. The participants (n=22) consumed grapefruit juice twice daily for 3weeks followed by a 2-week washout period. Blood samples for measurements of 4OHC and the non-CYP3A4-derived oxysterols 24-hydroxycholesterol (24OHC) and 27-hydroxycholesterol (27OHC), as well as lathosterol and total cholesterol, were drawn on days 0, 7, 21, and 35. Median individual changes (ratios) in cholesterol-corrected 4OHC levels from baseline to weeks 1, 3, and 5 were 0.94 (P=0.2), 0.98 (P=0.3), and 0.97 (P=0.9), respectively. In comparison, median changes (ratios) in cholesterol-corrected levels of 24OHC at the same points were 1.01 (P=0.6), 0.98 (P=0.3), and 0.99 (P=0.5), and of 27OHC 1.01 (P=0.8), 0.97 (P=0.5), and 0.99 (P=0.2). Surprisingly, serum concentration of cholesterol was significantly reduced by approximately 5% after 1week (P=0.03), while median cholesterol-corrected levels of lathosterol increased significantly and persistently by approximately 15% during the whole 5-week period (P