Jiangsu Institute of Nuclear Medicine, QianRong Road #20, Wuxi, Jiangsu 214063, China.
Lipids Health Dis. 2014 Apr 9;13:66. doi: 10.1186/1476-511X-13-66.
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.
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.
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.
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.
γ-生育三烯酚（GT3）是维生素 E 的类似物，最近因其具有显著的健康益处而引起了越来越多的科学关注。研究表明，经皮下给予乳化 GT3 后具有长期的生物学效应。然而，这些作用是由于给药后早期 GT3 水平的增加还是在组织中积累后的持续功能尚不清楚。本研究通过高效液相色谱法（HPLC）结合荧光检测器，在皮下注射聚乙二醇（PEG-400）乳剂的 GT3 单次剂量后，检测不同组织中的 GT3 水平。先前的研究表明，GT3 对骨骼有良好的作用，并能抑制破骨细胞的形成。为了证实组织中积累的 GT3 具有持续的生物学活性，还评估了在 GT3 信号皮下注射后第 1、3、7 和 14 天，骨组织中核因子-κB 受体激活剂配体（RANKL）和骨保护素（OPG）基因表达，这在调节破骨细胞形成中起重要作用。
C57BL/6 雌性小鼠经皮下注射给予 GT3（100mg/kg 体重）与 PEG-400 乳剂。通过 HPLC 结合荧光检测器测定不同组织中的 GT3 水平。通过实时 PCR 测量基因表达。
GT3 主要积聚在脂肪组织和心脏组织中，在单次给药后，在骨骼组织中维持相对稳定的水平。在骨骼组织中积累的 GT3 显著抑制 db-cAMP 诱导的 RANKL 表达增加和 OPG 表达减少。
我们通过皮下给予 PEG 乳剂研究了 GT3 的组织分布，这是迄今为止从未报道过的。我们的研究结果表明，PEG 乳剂中的 GT3 在组织中积累能够发挥长期的生物学作用，并且具有治疗和预防骨质疏松症的治疗价值。
