TY - JOUR
T1 - Secretion of vitamin A and retinol-binding protein into plasma is depressed in rats by N-(4-hydroxyphenyl)retinamide (Fenretinide)
AU - Smith, J. E.
AU - Lawless, D. C.
AU - Green, M. H.
AU - Moon, R. C.
PY - 1992
Y1 - 1992
N2 - In clinical trials the cancer preventive drug N-(4- hydroxyphenyl)retinamide (HPR) markedly lowers plasma concentrations of retinol and retinol-binding protein (RBP). Five hours after injection of HPR (51 μmol/kg), serum concentrations of retinol and RBP were 33 and 42% lower, respectively, than control values in rats. Because the mean transit time for retinol disappearance from serum of HPR-treated rats (1.9 h) was similar to that for radiolabeled retinol in control rats in previous studies, plasma retinol turnover is apparently not accelerated by HPR treatment. To study the effects of HPR on the secretion of the retinol-RBP complex from liver, control or HPR-treated rats were injected with chylomicrons containing [3H]vitamin A and [14C]triglycerides. Both labels were rapidly cleared from plasma in the two groups. In control rats [3H]retinol concentrations began to increase in plasma after 30 min due to liver secretion of retinol bound to RBP. In HPR-treated rats, secretion was apparently inhibited because the amount of [3H]retinol bound to RBP at 4.66 h was only 2.6% of the control level. We conclude that HPR partially blocks the secretion of the retinol-RBP complex from liver and other tissues, and thus depresses plasma concentrations of vitamin A and RBP.
AB - In clinical trials the cancer preventive drug N-(4- hydroxyphenyl)retinamide (HPR) markedly lowers plasma concentrations of retinol and retinol-binding protein (RBP). Five hours after injection of HPR (51 μmol/kg), serum concentrations of retinol and RBP were 33 and 42% lower, respectively, than control values in rats. Because the mean transit time for retinol disappearance from serum of HPR-treated rats (1.9 h) was similar to that for radiolabeled retinol in control rats in previous studies, plasma retinol turnover is apparently not accelerated by HPR treatment. To study the effects of HPR on the secretion of the retinol-RBP complex from liver, control or HPR-treated rats were injected with chylomicrons containing [3H]vitamin A and [14C]triglycerides. Both labels were rapidly cleared from plasma in the two groups. In control rats [3H]retinol concentrations began to increase in plasma after 30 min due to liver secretion of retinol bound to RBP. In HPR-treated rats, secretion was apparently inhibited because the amount of [3H]retinol bound to RBP at 4.66 h was only 2.6% of the control level. We conclude that HPR partially blocks the secretion of the retinol-RBP complex from liver and other tissues, and thus depresses plasma concentrations of vitamin A and RBP.
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U2 - 10.1093/jn/122.10.1999
DO - 10.1093/jn/122.10.1999
M3 - Article
C2 - 1388202
AN - SCOPUS:0026705170
SN - 0022-3166
VL - 122
SP - 1999
EP - 2009
JO - Journal of Nutrition
JF - Journal of Nutrition
IS - 10
ER -