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 (T max) 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.
Original language | English (US) |
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Pages (from-to) | 157-163 |
Number of pages | 7 |
Journal | Pharmacology |
Volume | 83 |
Issue number | 3 |
DOIs | |
State | Published - Feb 2009 |
Externally published | Yes |
Keywords
- Pancreatic cancer
- Pharmacokinetics
- Tissue distribution
- δ-Tocotrienol
- δ-Tocotrienol, mice
ASJC Scopus subject areas
- Pharmacology