Distribution and metabolism of sphingosine in skin after oral administration to mice.
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.
Ueda
Osamu
O
Functional Food Research & Development Center, Shiseido Co., Ltd, Yokohama, Japan. osamu.ueda＠to.shiseido.co.jp
Uchiyama
Taro
T
Nakashima
Masaya
M
D000284:Administration, Oral; D000825:Animal Structures / Q000378:metabolism; D000818:Animals; D019540:Area Under Curve; D002478:Cells, Cultured; D002518:Ceramides / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D020405:Dermis / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism; D005243:Feces / Q000737:chemistry; D005963:Glucosylceramides / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D012867:Skin / Q000378:metabolism*; D013110:Sphingosine / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism* / Q000652:urine; D053719:Tandem Mass Spectrometry; D014018:Tissue Distribution
D002518:Ceramides; D005963:Glucosylceramides; D013110:Sphingosine