Affiliations: Laboratory of Nutritional Biochemistry, Institute of
Microbiology and Biochemistry, National Taiwan University, Taipei,
Taiwan | Department of Health and Nutrition, Chia-Nan
University of Pharmacy and Science, Tainan, Taiwan
Abstract: In this study, the CYP3A inducer pregnenolone-16α-carbonitrile
(PCN) and the CYP3A inhibitor ketoconazole (KCZ) were
used to investigate whether the metabolism of α-tocopherol to
its metabolite, α-carboxyethyl
hydroxychroman (α-CEHC), is CYP3A-dependent in rats.
In experiment 1, two groups of Wistar rats were fed for 3 wk with either a
basal diet (containing 50~ppm of α-tocopherol) or the
same diet containing 10-fold more α-tocopherol. In the
last 3 days, each group was divided into 2 subgroups which were given a single
i.p. injection of either PCN at 75 mg/kg/d (P50 & P500 groups) or DMSO
(D50 & D500 groups). The liver TBARS concentration was highest in the
P50 group. Two-way ANOVA analysis showed that α-tocopherol
levels in the plasma and liver were both significantly
decreased by PCN (p < 0.0001), as were α-CEHC
levels in the urine (p = 0.0004). In
experiment 2, α-tocopherol levels in the liver were
increased and α-CEHC excretion in the urine decreased
in the Wistar rats fed with KCZ containing diet. In experiment 3, Wistar rats
administered with dexamethasone (DEX) significantly decreased α-tocopherol
levels in the plasma and liver and α-CEHC
levels in the urine. These data showed CYP3A is not a major
contributor of the metabolism of α-tocopherol to
α-CEHC. Nevertheless, vitamin E status was markedly
reduced by CYP3A inducers due to increased lipid peroxidation and this would
increase the consumption of α-tocopherol in the
liver.
