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Profiling the hepatic accumulation and clearance of α‐retinol and α‐retinyl ester in α‐retinyl acetate‐dosed rats
Author(s) -
Dever Joseph T,
Riabroy Napaporn,
Tanumihardjo Sherry A
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.333.3
Subject(s) - retinol , retinyl acetate , chemistry , metabolite , medicine , endocrinology , vitamin , retinyl palmitate , weanling , pharmacokinetics , toxicity , biochemistry , biology
α‐Retinol (αR) is a bioactive retinol analog and α‐carotene metabolite that does not bind to serum retinol‐binding protein. In this study, α‐retinyl acetate (αRA) was given to vitamin A‐deficient weanling rats as a single, oral dose (3.5 μmol) to quantify serum and liver accumulation and clearance (0–14 d) of αR and α‐retinyl ester (αRE). Serum total αR concentrations peaked 1.5 h post‐dose (5.3 ± 0.7 μmol/L, mean ± SEM) as α‐retinyl palmitate (αRP) (47%), α‐retinyl sterate (αRS) (31%), minor αREs (19%), and αR (3%). αRP serum concentrations dropped to 0.028 ± 0.004 μmol/L 2 d post‐dose but remained steady at 4, 7, and 14 d post‐dose. Liver total αR concentrations peaked 1 d post‐dose (0.21 ± 0.02 μmol/g liver) as αRP (76%), αR (11%), αRS (8%), and minor αREs (5%). Whole liver total αR did not decrease from 1–14 d post‐dose. In rats given 3.5 μmol αRA/d for 21 d, total αR concentrations reached 2.2 ± 0.1 μmol/g liver with no observable toxicity, then decreased to 1.5 ± 0.1 μmol/g liver after 14 d. These data suggest that αRP is recirculated from the liver, perhaps in LDL, which may contribute to its hepatic clearance and bioactivity. Supported by USDA‐NRI 2007‐35200‐17729 and NIH T32 DK007665