Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Nutrients. 2012 Jun;4(6):467-90. doi: 10.3390/nu4060467. Epub 2012 Jun 6.
Vitamin E isoforms are essential nutrients that are widely used as dietary supplements and therapeutic agents for a variety of diseases. However, their pharmacokinetic (PK) properties remain poorly characterized, and high dosage animal studies may provide further information on their in vivo functions and pharmacological effects. In this study, alpha-tocopherol (α-toc) and delta-tocopherol (δ-toc) levels were measured in mouse plasma and tissues following their high dosage dietary supplementation. Average α-toc levels at 5, 10 and 20 g α-toc/kg diet increased over baseline levels 6-fold in plasma, 1.6-fold in brain, and 4.9-fold in liver. These elevated α-toc concentrations remained constant from 5 to 20 g α-toc/kg diet, rather than showing further increases across these dosages. No α-toc-related toxicity occurred at these high dosages, and strain-specific differences in liver and brain α-toc levels between Balb/cJ and C57Bl/6J mice were observed. Relatively high-dosage administration of dietary δ-toc for 1 or 4 weeks resulted in 6-30-fold increases in plasma and liver levels between dosages of 0.33 and 1.67 g δ-toc/kg diet. Co-administration of sesamin with δ-toc further increased δ-toc levels between 1.3- and 14-fold in plasma, liver, and brain. These results provide valuable PK information on high dosage α-toc and δ-toc in mouse and show that supplementation of sesamin with δ-toc further increases δ-toc levels over those seen with δ-toc supplementation alone.
维生素 E 异构体是必需的营养物质，被广泛用作膳食补充剂和治疗各种疾病的药物。然而，它们的药代动力学（PK）特性仍未得到充分描述，高剂量动物研究可能提供更多关于其体内功能和药理作用的信息。在这项研究中，在高剂量饮食补充后，测量了小鼠血浆和组织中的α-生育酚（α-Toc）和δ-生育酚（δ-Toc）水平。在血浆中，α-Toc 的平均水平在 5、10 和 20 g α-Toc/kg 饮食时比基线水平增加了 6 倍，在大脑中增加了 1.6 倍，在肝脏中增加了 4.9 倍。这些升高的α-Toc 浓度在 5 至 20 g α-Toc/kg 饮食之间保持不变，而不是在这些剂量下进一步增加。在这些高剂量下没有发生与α-Toc 相关的毒性，并且在 Balb/cJ 和 C57Bl/6J 小鼠的肝脏和大脑中观察到了与α-Toc 水平相关的、特定于品系的差异。相对高剂量的膳食 δ-Toc 给药 1 或 4 周，导致血浆和肝脏水平在 0.33 和 1.67 g δ-Toc/kg 饮食剂量之间增加了 6-30 倍。Sesamin 与 δ-Toc 共同给药进一步使血浆、肝脏和大脑中的 δ-Toc 水平增加了 1.3-14 倍。这些结果为小鼠中高剂量 α-Toc 和 δ-Toc 的 PK 提供了有价值的信息，并表明 Sesamin 与 δ-Toc 联合补充可使 δ-Toc 水平进一步高于单独补充 δ-Toc 时的水平。
