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Pancreatic Tissue Distribution, Pharmacokinetics and Toxicity of Bioactive delta‐tocotrienol, a Potential Anti‐tumor Bioactive Food Component, in Mice
Author(s) -
Husain Kazim,
Hutchinson Sean Z,
Francois Rony A,
Neuger Anthony M,
Lush Richard,
Sebti Said,
Malafa Mokenge P
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.922.3
Subject(s) - tocotrienol , bioavailability , pharmacokinetics , pharmacology , oral administration , pancreatic cancer , pancreas , vitamin e , toxicity , chemistry , tocopherol , medicine , antioxidant , cancer , biochemistry
Tocotrienols are natural vitamin E compounds in foods such as cereal. They have been shown to inhibit cancer cell growth and survival. Recently, we observed that δ‐tocotrienol is the most active tocotrienol against pancreatic cancer. The objective of this study was to determine the oral bioavailability of δ‐tocotrienol in mice pancreas and in the tumor. Mice (4–5 weeks old) were treated orally with vehicle (PBS/ethanol extracted olive oil), 50 mg/kg or 100 mg/kg dose of δ‐tocotrienol. Plasma and tissues were isolated at different time points and δ‐tocotrienol was analyzed by HPLC using fluorescence detection. The results show that the peak plasma concentration (C max ) was 57 μM and the T max was 2 h. The maximum concentration of δ‐Tocotrienol was achieved at 2 h in the liver and at 8 h in the pancreas. The δ‐tocotrienol was cleared from plasma and liver within 24 h but had delayed clearance from the pancreas. Interestingly we found that δ‐tocotrienol was 10‐fold more concentrated in the pancreas than in the tumor tissue. We also observed no toxicity due to δ‐tocotrienol administration as documented by normal weight gain of the mice with no mortality. Our data suggests that δ‐tocotrienol is safe, and orally bioavailable in the pancreatic tissue of mice at levels which predicts bioactivity against neoplastic cells. We conclude that δ‐tocotrienol should be investigated for the prevention and treatment of pancreatic cancer.