Journal of Lipid Research, Vol 31, 183-190, Copyright © 1990 by Lipid Research, Inc.
Metabolism of very low density lipoproteins in rats with isotretinoin (13-cis retinoic acid)-induced hyperlipidemia
S Gustafson, C Vahlquist, L Sjoblom, A Eklund and A Vahlquist
Department of Medical and Physiological Chemistry, University of Uppsala, Sweden.
A significant rise in plasma triacylglycerols from the control level of
0.89 mmol/l to 1.88 mmol/l (P less than 0.001) was observed in male
Sprague-Dawley rats treated for 11 days with isotretinoin (oral dosing; 10
mg/day). This rise was due to an increased level of plasma very low density
lipoproteins (VLDL). When VLDL from untreated rats were labeled with
125I-labeled tyramine-cellobiose and injected intravenously into rats
treated for 10 days with isotretinoin (n = 6) and in control rats (n = 6),
it was found that the disappearance of radioactivity from the blood was
dramatically retarded in the treated animals. The disappearance could be
divided into two phases, a rapid (alpha) phase dominated the first 5 min
and was followed by a slower (beta) phase. The half-life of the beta-phase
increased significantly from 53 +/- 7 min in the controls, to 120 +/- 62
min after isotretinoin. VLDL prepared from isotretinoin-treated animals (n
= 6) had about the same half-life in control animals (62 +/- 8 min) as had
ordinary VLDL. The elimination of tracer from the blood was mainly due to
uptake by the liver. The amount of radioactivity in the liver after 30 min
of circulation was significantly reduced from 34 +/- 7% of injected dose in
controls to 24 +/- 5% in the isotretinoin group (P = 0.013). The uptake in
other organs was less than 3% per organ and was essentially unaffected by
the treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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