1. Vitamin E δ-Tocotrienol Levels in Tumor and Pancreatic Tissue of Mice after Oral Administration
- Author
-
Sean Z. Hutchinson, Domenico Coppola, Richard Lush, Anthony Neuger, Said M. Sebti, Rony A. Francois, Mokenge P. Malafa, and Kazim Husain
- Subjects
medicine.medical_specialty ,medicine.medical_treatment ,Transplantation, Heterologous ,Administration, Oral ,Mice, Nude ,Biology ,Neuroprotection ,Mice ,chemistry.chemical_compound ,Pharmacokinetics ,Oral administration ,Cell Line, Tumor ,Internal medicine ,medicine ,Animals ,Vitamin E ,Tissue Distribution ,Pancreas ,Pharmacology ,Original Paper ,General Medicine ,biochemical phenomena, metabolism, and nutrition ,Pancreatic Neoplasms ,Transplantation ,Endocrinology ,medicine.anatomical_structure ,Liver ,chemistry ,Toxicity ,Female ,Tocotrienol ,Neoplasm Transplantation ,Half-Life - Abstract
Tocotrienols are natural vitamin E compounds that are known to have a neuroprotective effect at nanomolar concentration and anti-carcinogenic effect at micromolar concentration. In this report, we investigated the pharmacokinetics, tumor and pancreatic tissue levels, and toxicity of δ-tocotrienol in mice because of its anti-tumor activity against pancreatic cancer. Following a single oral administration of δ-tocotrienol at 100 mg/kg, the peak plasma concentration (Cmax) was 57 ± 5 μmol/l, the time required to reach peak plasma concentration (Tmax) was 2 h and plasma half-life (t1/2) was 3.5 h. The δ-tocotrienol was cleared from plasma and liver within 24 h, but delayed from the pancreas. When mice were fed δ-tocotrienol for 6 weeks, the concentration in tumor tissue was 41 ± 3.5 nmol/g. This concentration was observed with the oral dose (100 mg/kg) of δ-tocotrienol which inhibited tumor growth by 80% in our previous studies. Interestingly, δ-tocotrienol was 10-fold more concentrated in the pancreas than in the tumor. We observed no toxicity due to δ-tocotrienol as mice gained normal weight with no histopathological changes in tissues. Our data suggest that bioactive levels of δ-tocotrienol can be achieved in the pancreas following oral administration and supports its clinical investigation in pancreatic cancer.
- Published
- 2009
- Full Text
- View/download PDF