Tissue distribution of emulsified γ-tocotrienol and its long-term biological effects after subcutaneous administration

Lili Deng,Yuedi Ding,Quancheng Chen,Yu Wu,Qiang Fu,Ying Peng,Meilin Yang

doi:10.1186/1476-511x-13-66

Abstract

Backgroundγ-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.MethodsC57BL/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.ResultsGT3 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.ConclusionsWe 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.

Highlights

Vitamin E, one of the essential micronutrients and a known antioxidant, includes two groups of closely related fat-soluble compounds, the tocopherols and tocotrienols, each with the four analogues, α, β, γ, and δ
As GT3 is the sole vitamin E analogue in our experimental samples, a reversed-phase high performance liquid chromatography (HPLC) method with a fluorescence detector was utilized for GT3 analysis in our study
Our results showed that RANKL was increased and OPG was decreased in mRNA levels after administration of db-cAMP; accumulated GT3 in bone tissues inhibited RANKL expression and blocked the down-regulation of OPG, even on day 14 after the single-dose of emulsified GT3 supplementation (Figure 3)

Summary

Introduction

Vitamin E, one of the essential micronutrients and a known antioxidant, includes two groups of closely related fat-soluble compounds, the tocopherols and tocotrienols, each with the four analogues, α, β, γ, and δ. Tocotrienols have gained increasing scientific interest during recent years as they have been reported to possess certain biology activities that were not observed in tocopherols [4] This is especially true for γ-tocotrienol (GT3), which is abundant in palm oil and rice bran [5,6], as it provides significant health benefits, including anticancer [7,8,9,10], anticholesterolemic [11,12], antihypertensive [13], and antiatherosclerotic effects [14], as well as acting as a potent antioxidant [15,16]. All of these studies have shown γtocotrienol health benefits to be significantly greater than those of α-tocopherol

Methods

Results

Conclusion