Biliary metabolites of all-trans-retinoic acid in the rat

doi:10.1016/0003-9861(83)90185-6

Archives of Biochemistry and Biophysics

Volume 224, Issue 1, 1 July 1983, Pages 13-18

https://doi.org/10.1016/0003-9861(83)90185-6 Get rights and content

Abstract

Biliary metabolites from physiological doses of all-trans-[10-³H]retinoic acid were examined in normal and vitamin A-deficient rats. The bile from normal and vitamin A-deficient rats contained approximately 60% of the administered dose following a 24-h collection period. However, vitamin A-deficient rats show a 6-h delay in the excretion of radioactivity compared to normal rats. Retinoyl-β-glucuronide excretion was particularly sensitive to the vitamin A status of the rats. In normal rats, retinoyl-β-glucuronide reached a maximum concentration of 235 pmol/ml of bile 2 h following the dose and then rapidly declined. Vitamin A-deficient rats show a relatively constant concentration of this metabolite (100–150 pmol/ml of bile) over a 10-h collection period. Retinoic acid excretion was low in both normal and deficient rats. The concentration of retinotaurine, a recently identified biliary metabolite, was approximately equal to retinoyl-β-glucuronide in normal rats and appeared in the bile 2 h later than the glucuronide.

References (18)

M. Zile et al.
J. Nutr
(1968)
R.D. Zachman et al.
J. Lipid Res
(1966)
B.N. Swanson et al.
Biochem. Pharmacol
(1981)
C.A. Frolik et al.
Arch. Biochem. Biophys
(1981)
M.H. Zile et al.
J. Biol. Chem
(1982)
H.F. DeLuca et al.
J. Nutr
(1963)
M.H. Zile et al.
J. Biol. Chem
(1982)
A.B. Roberts et al.
J. Biol. Chem
(1979)
A.B. Roberts et al.
Arch. Biochem. Biophys
(1980)

There are more references available in the full text version of this article.

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^☆: This work was supported by program project Grant AM-14881 from the National Institutes of Health, a predoctoral fellowship from Procter and Gamble, and by the Harry Steenbock Research Fund of the Wisconsin Alumni Research Foundation.

²: Present address: Procter and Gamble Co., Research and Development Department, Miami Valley Laboratories, P.O. Box 39175, Cincinnati, Ohio 45247.

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Biliary metabolites of all-trans-retinoic acid in the rat☆

Abstract

J. Nutr

J. Lipid Res

Biochem. Pharmacol

Arch. Biochem. Biophys

J. Biol. Chem

J. Nutr

J. Biol. Chem

J. Biol. Chem

Arch. Biochem. Biophys