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

Introduction: 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. Aim: To determine the kinetic of plasma lipids and lipoproteins following injection of tyloxapol over a period of two weeks. Materials and Methods: Fifteen male rats were starved overnight 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). Results: 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. Conclusion: 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.