PURPOSE: We examined the effects of apolipoprotein B (apoB) on the disposition kinetics of alpha-tocopherol by using apoB knockout mice. METHODS: The concentrations of alpha-tocopherol in plasma and tissues were measured by gas chromatography-mass spectrometry. RESULTS: In apob (-/-) mice, the endogenous levels of alpha-tocopherol in plasma and tissues (except liver) were significantly lower, and the liver concentration was significantly higher than those in wild-type mice. After single i.v. administration of alpha-tocopherol (25 mg/kg), the area under the plasma concentration-time curve (AUC) and the distribution volume at steady state were significantly decreased, whereas the total clearance of alpha-tocopherol was significantly increased in apob (-/-) vs. wild-type mice. Alpha-Tocopherol was highly distributed to the liver, compared with other tissues. After an oral administration of alpha-tocopherol (100 mg/kg), the intestinal absorption of alpha-tocopherol was very low in apoB knockout mice, as the value of AUC0-32h for apob (-/-) mice (17.7 +/- 8.3 (microg h/mL) was significantly less than that for apob (+/+) wild-type mice (96.5 +/- 15.8 microg h/mL, mean +/- SD of five experiments, p < 0.01). The biliary excretion of alpha-tocopherol was significantly greater in apob (+/-) mice than in apob (+/+) mice. CONCLUSIONS: These results show that apoB plays a role in hepatic secretion and intestinal absorption of alpha-tocopherol.
PURPOSE: We examined the effects of apolipoprotein B (apoB) on the disposition kinetics of alpha-tocopherol by using apoB knockout mice. METHODS: The concentrations of alpha-tocopherol in plasma and tissues were measured by gas chromatography-mass spectrometry. RESULTS: In apob (-/-) mice, the endogenous levels of alpha-tocopherol in plasma and tissues (except liver) were significantly lower, and the liver concentration was significantly higher than those in wild-type mice. After single i.v. administration of alpha-tocopherol (25 mg/kg), the area under the plasma concentration-time curve (AUC) and the distribution volume at steady state were significantly decreased, whereas the total clearance of alpha-tocopherol was significantly increased in apob (-/-) vs. wild-type mice. Alpha-Tocopherol was highly distributed to the liver, compared with other tissues. After an oral administration of alpha-tocopherol (100 mg/kg), the intestinal absorption of alpha-tocopherol was very low in apoB knockout mice, as the value of AUC0-32h for apob (-/-) mice (17.7 +/- 8.3 (microg h/mL) was significantly less than that for apob (+/+) wild-type mice (96.5 +/- 15.8 microg h/mL, mean +/- SD of five experiments, p < 0.01). The biliary excretion of alpha-tocopherol was significantly greater in apob (+/-) mice than in apob (+/+) mice. CONCLUSIONS: These results show that apoB plays a role in hepatic secretion and intestinal absorption of alpha-tocopherol.
Authors: D Sharp; L Blinderman; K A Combs; B Kienzle; B Ricci; K Wager-Smith; C M Gil; C W Turck; M E Bouma; D J Rader Journal: Nature Date: 1993-09-02 Impact factor: 49.962