Orally ingested (13)C(2)-retinol is incorporated into hepatic retinyl esters in a nonhuman primate (Macaca mulatta) model of hypervitaminosis A.
The mechanism responsible for the metabolism of vitamin A during hypervitaminosis is largely unknown. This study investigated hepatic (13)C-retinol uptake in hypervitaminotic A rhesus monkeys. We hypothesized that individual retinyl esters would be enriched in (13)C after a physiologic dose of (13)C(2)-retinyl acetate, thus suggesting de novo in vivo hepatic retinol esterification. Male rhesus macaques (n = 16; 11.8 +/- 2.9 y) each received 3.5 micromol 14, 15-(13)C(2)-retinyl acetate. Blood was drawn at baseline and 5 h and 2, 4, 7, 14, 21, and 28 d after administration. Liver biopsies were collected 7 d before and 2 d after dose administration (n = 4) and at 7, 14, and 28 d after dose administration (n = 4 per time point). (13)C enrichments of retinol and retinyl esters HPLC-purified from liver samples were measured by using gas chromatography-combustion-isotope ratio mass spectrometry. (13)C enrichment of total vitamin A and individual retinyl esters were significantly greater 2 d after dose administration compared with baseline levels. In contrast, the concentration of isolated retinyl esters did not always increase 2 d after treatment. Given that the liver biopsy site differed between monkeys, these data suggest that the accumulation of hepatic retinyl esters is a dynamic process that is better represented by combining analytical techniques. This sensitive methodology can be used to characterize vitamin A trafficking after physiologic doses of (13)C-retinol. In this nonhuman primate model of hypervitaminosis A, hepatic retinyl esters continued to accumulate with high liver stores.
University of Wisconsin-Madison, USA.
Anne L
AL
Escaron
Sherry A
SA
Tanumihardjo
D000284:Administration, Oral; D000818:Animals; D002247:Carbon Isotopes; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008401:Gas Chromatography-Mass Spectrometry; D006986:Hypervitaminosis A / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008253:Macaca mulatta; D008297:Male; D014801:Vitamin A / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics
D002247:Carbon Isotopes; D014801:Vitamin A