Summary
Pluronic L-81 (L-81), a non-ionic hydrophobic surfactant, is a powerful inhibitor
of the secretion of lipid-transporting chylomicrons from intestinal epithelial cells
to lymph. Since the other major organ that secretes lipoproteins into the circulation
is the liver, whose principal lipid secretory product is very low density lipoprotein
(VLDL), we tested the hypothesis that L-81 will also inhibit hepatic lipid secretion.
Rats were fasted so that they had little lipid input from the intestine. We then administered
Triton WR-1339 (tyloxapol) intravenously to block peripheral utilization of VLDL,
causing plasma lipids to rise rapidly. Some animals were also given L-81 intravenously
to test whether the L-81 would retard the tyloxapol-induced rise in plasma lipids.
Administration of tyloxapol alone (250 mg/kg) increased plasma triglyceride, phospholipid
and cholesterol concentrations considerably. Simultaneous administration of a small
dose of L-81 (6 mg/kg) markedly reduced the rise in plasma triglyceride, particularly
in the first hour (by 45%). L-81 also diminished the rise in plasma phospholipid and
cholesterol, but to a lesser extent (30%). In the fasting rat, most of the plasma
triglyceride is in VLDL; therefore, L-81 probably acts by decreasing the secretion
of hepatic VLDL. Thus, Pluronic L-81 may be a useful tool for examining the secretion
and metabolism of hepatic lipoproteins, in particular, VLDL.
Key-Words
Plasma Triglyceride - Plasma Cholesterol - Plasma Phospholipid - Very Low Density
Lipoprotein (VLDL) - Hepatic Lipid Secretion - Tyloxapol