Tissue distribution of emulsified γ-tocotrienol and its long-term biological effects after subcutaneous administration.
BACKGROUND
γ-tocotrienol (GT3), an analogue of vitamin E, has gained increasing scientific interest recently as it provides significant health benefits. It has been shown that emulsified GT3, after subcutaneous administration, has long-term biological effects. However, whether the effects are due to the increase of GT3 level in the early phase following administration or the persistent functions after accumulation in tissues is unknown. This study was conducted to determine the levels of GT3 in different tissues by high performance liquid chromatography (HPLC) with a fluorescence detector after a single-dose of GT3 with polyethylene glycol (PEG-400) emulsion via subcutaneous injection. Previous studies have explored that GT3 has favorable effects on bone and can inhibit osteoclast formation. To confirm the persistent biological activity of accumulated GT3 in tissues, receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) gene expressions, which have an important role in regulating osteoclast formation, were also evaluated in bone tissue on day 1, 3, 7 and 14 after a signal subcutaneous injection of GT3.


METHODS
C57BL/6 female mice were administrated GT3 (100 mg/kg body weight) with PEG-400 emulsion by subcutaneous injection. GT3 levels in different tissues were determined by HPLC with a fluorescence detector. Gene expressions were measured by real-time PCR.


RESULTS
GT3 predominantly accumulated in adipose and heart tissue, and was maintained at a relatively stable level in bone tissues after a single-dose administration. Accumulated GT3 in bone tissues significantly inhibited the increase in RANKL expression and the decrease in OPG expression induced by db-cAMP.


CONCLUSIONS
We investigated the tissue distribution of GT3 with PEG emulsion by subcutaneous administration, which has never been reported so far. Our results suggest that GT3 with PEG emulsion accumulated in tissues is able to carry out a long-term biological effect and has therapeutic value for treating and preventing osteoporosis.
Lili
L
Deng
Ying
Y
Peng
Yu
Y
Wu
Meilin
M
Yang
Yuedi
Y
Ding
Quancheng
Q
Chen
Jiangsu Institute of Nuclear Medicine, QianRong Road #20, Wuxi, Jiangsu 214063, China. fuqiang@jsinm.org.
Qiang
Q
Fu
D000818:Animals; D002839:Chromans / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004655:Emulsions / Q000737:chemistry*; D005260:Female; D007279:Injections, Subcutaneous; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism; D053244:Osteoprotegerin / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry; D053245:RANK Ligand / Q000378:metabolism; D014810:Vitamin E / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
D002839:Chromans; D004655:Emulsions; D053244:Osteoprotegerin; D053245:RANK Ligand; D014810:Vitamin E; D011092:Polyethylene Glycols; C013649:plastochromanol 8