Functional Food Research & Development Center, Shiseido Co., Ltd, Yokohama, Japan. osamu.ueda＠to.shiseido.co.jp
Drug Metab Pharmacokinet. 2010;25(5):456-65. doi: 10.2133/dmpk.dmpk-10-rg-038. Epub 2010 Sep 22.
In this study, (3)H- or (13)C(2),D(2)-sphingosine (SPH) was orally administered to mice to assess absorption, mass balance, tissue distribution, and metabolites in the skin. The blood concentration of (3)H-SPH showed a Tmax of 10.7 hr. The radioactivity in the skin reached 763.4 ng eq./g tissue at 12 hr, and decreased to 181.7 ng eq./g tissue at 168 hr. The concentration of radioactivity at 12 hr was 577.6 and 100.7 ng eq./g tissue in the dermis and epidermis, respectively. Thereafter, the dermis concentration decreased to 158.5 ng eq./g tissue, while the epidermis concentration increased to 298.8 ng eq./g tissue, suggesting that radioactivity moves from the dermis to the epidermis. Unchanged SPH along with lipophilic metabolites was detected in the skin of mice exposed orally to (3)H- or (13)C(2),D(2)-SPH. Moreover, in an in vitro study using human skin keratinocytes, a (13)C(2),D(2)-SPH-treatment resulted in the intracellular production of glucosylceramides (GlcCer) and ceramides (Cer) containing labeled-SPH. These results indicate the followings: first, that SPH is absorbed through the digestive tract and distributed to the skin; second, it is transferred from the dermis to the epidermis; and third, SPH is partly distributed to the skin in an unchanged form, and some of the distributed compounds are converted into GlcCer and Cer by biosynthesis.
在这项研究中，（3）H-或（13）C（2），D（2）-神经酰胺（SPH）经口给予小鼠，以评估其在肠道中的吸收、物质平衡、组织分布和在皮肤中的代谢物。（3）H-SPH 的血液浓度达到 Tmax 的时间为 10.7 小时。在 12 小时时，皮肤中的放射性达到 763.4ng eq./g 组织，在 168 小时时降至 181.7ng eq./g 组织。在 12 小时时，真皮和表皮中的放射性浓度分别为 577.6 和 100.7ng eq./g 组织。此后，真皮中的浓度降至 158.5ng eq./g 组织，而表皮中的浓度增加到 298.8ng eq./g 组织，表明放射性物质从真皮转移到表皮。在经口给予（3）H-或（13）C（2），D（2）-SPH 的小鼠皮肤中检测到未改变的 SPH 以及亲脂性代谢物。此外，在使用人皮肤角质形成细胞的体外研究中，（13）C（2），D（2）-SPH 处理导致细胞内产生葡糖基神经酰胺（GlcCer）和含有标记-SPH 的神经酰胺（Cer）。这些结果表明：首先，SPH 通过消化道吸收并分布到皮肤中；其次，它从真皮转移到表皮；第三，SPH 以未改变的形式部分分布到皮肤中，一些分布的化合物通过生物合成转化为 GlcCer 和 Cer。
