The Long Term Kinetic of Plasma Lipids and Lipoproteins in Tyloxapol Injected Rats.

Abstract

The level of plasma triglyceride is balanced by the rate of secretion into and clearance from the plasma. Tyloxapol (Triton WR1339) is a nonionic detergent that inhibits lipoprotein lipase and hence clearance of triglyceride from the plasma. To determine the kinetic of plasma lipids and lipoproteins following injection of tyloxapol over a period of two weeks. Fifteen male rats were starved over-night and injected intravenously with tyloxapol (400mg/kg). Blood samples were taken in three steps as, the early (1-6 hours), the middle (1-2 days) and the third (3-9 days) phase. Plasma total cholesterol and triglyceride were measured by enzymatic methods and total phospholipids were analysed as molybdenum blue. Serum lipoproteins were fractionated by electrophoresis on agarose gel (Sebia Inc). The changes of plasma lipids following tyloxapol injection showed three distinctive phases. The early phase lasts at least 6 hours, and the concentrations of triglyceride, total cholesterol and phospholipids increased linearly. The rate of triglyceride secretion was 259.7 ± 8.1 mg/h.dl in this phase, which was comparable to the mean rate of 250.6 ± 37.0 mg/h.dl or 102.8 ± 15.2 mg/h.kg body in starved male rat. During the next 48 hour the lipids continued to accumulate but at a lower rate, and the levels of triglyceride, cholesterol and total phospholipids rose up to about 3200, 586 and 715 mg/dl respectively. In the last phase, the levels of plasma lipids decreased toward the basal levels after 5 days. In serum lipoprotein electrophoresis, the VLDL and LDL increased and HDL fraction disappeared simultaneously during the initial 2 hours of tyloxapol injection. The VLDL fell down toward the normal range, preceded to the reappearance of HDL during 5 days. A single intravenous injection of tyloxapol shows three distinctive phases. In the early phase, triglyceride accumulates linearly and the rate of its increment in plasma is a good estimate of the rate of VLDL secretion from the liver.