Delivery of Orally Supplemented Alpha-Tocotrienol to Vital Organs of Rats and Tocopherol-Transport Protein Deficient Mice

Free Radic Biol Med. 2005 Nov 15;39(10):1310-9. doi: 10.1016/j.freeradbiomed.2005.06.013.

Abstract

The natural vitamin E tocotrienol (TCT) possesses biological properties not shared by tocopherols (TCP). Nanomolar alpha-TCT, not alpha-TCP, is potently neuroprotective (JBC 275:13049; 278:43508). Tocopherol-transport protein (TTP) represents the primary mechanism for maintaining normal alpha-TCP concentrations in plasma and extrahepatic tissues. TTP primarily transports alpha-TCP and has low affinity for alpha-TCT. There are no studies that have investigated tissue delivery of alpha-TCT when orally gavaged on a long-term basis. A long-term study was conducted to examine the effects of alpha-TCT or alpha-TCP supplementation, either alone or in combination, on tissue levels. Rats were maintained on a vitamin E-deficient diet and gavaged with alpha-TCT or alpha-TCP alone or in combination. Five generations of rats were studied over 60 weeks. TTP-deficient mice were supplemented with TCT and bred to examine tissue delivery of oral alpha-TCT. Orally supplemented alpha-TCT was effectively delivered to most tissues over time. When co-supplemented, alpha-TCP outcompeted alpha-TCT for transport systems delivering vitamin E to tissues. To evaluate the significance of TTP in alpha-TCT delivery to tissues, tissue levels of alpha-TCT in supplemented TTP-deficient mice were studied. alpha-TCT was transported to several vital organs in TTP-deficient mice. alpha-TCT restored fertility in TTP-deficient mice. In sum, orally supplemented alpha-TCT was successfully delivered to several vital organs. The transport efficiency of alpha-TCT to tissues may be maximized by eliminating the co-presence of alpha-TCP in the oral supplement. Examination of whether alpha-TCT may benefit humans suffering from neurological disorders because of congenital TTP deficiency is warranted.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Animals
  • Antioxidants / metabolism
  • Biological Transport
  • Carrier Proteins / metabolism
  • Female
  • Humans
  • Lung / metabolism
  • Male
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Muscle, Skeletal / pathology
  • Neuroprotective Agents / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Tissue Distribution
  • Tocopherols / metabolism
  • Tocopherols / pharmacology*
  • Tocotrienols
  • Vitamin E / administration & dosage
  • Vitamin E / analogs & derivatives*
  • Vitamin E / metabolism
  • Vitamin E / pharmacology

Substances

  • Antioxidants
  • Carrier Proteins
  • Neuroprotective Agents
  • Tocotrienols
  • alpha-tocopherol transfer protein
  • Vitamin E
  • tocotrienol, alpha
  • Tocopherols