Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2003
Poloxamer 407-mediated alterations in the activities of enzymes regulating lipid metabolism in rats.
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Wasan Kishor M, Subramanian Ramaswamy, Kwong Mona, Goldberg Ira J, Wright Thamrah, Johnston Thomas P
Аннотация
PURPOSE: Recently, the P-407-treated mouse was established as a useful animal model of hyperlipidemia and atherosclerosis. The present study was aimed to determine whether P-407-induced hyperlipidemia in the rat is associated with alterations in the activities of enzymes responsible for lipid metabolism.
METHODS AND RESULTS: Rats were made hyperlipidemic by i.p. injection of 1.0 g/kg P-407 and blood samples collected 24 h after administration of P-407. Plasma from P-407-treated rats demonstrated 7- and 13-fold increases in cholesterol and triglycerides, respectively (p < 0.001). The plasma lecithin cholesterol acyl transferase (LCAT) activity in these animals was 4-5-fold greater than control animals (p < 0.05). Further, the plasma cholesteryl ester transfer protein (CETP) activity in P-407-treated rats was increased by approximately 25%, which was inhibited by > 50% in the presence of TP2, a monoclonal anti-CETP antibody (27.03 +/- 3.16 vs. 10.87 +/- 3.23; p < 0.05). The plasma CETP protein levels were also increased by 5-6-fold in P-407-treated animals (control 0.35 +/- 0.17 vs. P-407 treated 1.87 +/- 0.35 ug/ml, p < 0.05). However, the plasma hepatic lipase (HL) (control 49.2 +/- 3.1 vs. P-407-treated 2.0 +/- 0.38 umol/ml/h; p < 0.001) and lipoprotein lipase (LPL) (control 45.9 +/- 0.09 vs. P-407-treated 2.03 +/- 0.38 mol/ml/hr; p<0.001) activities in these animals were significantly inhibited.
CONCLUSIONS: In summary, P-407-induced hyperlipidemia in rats is associated with alterations in plasma LCAT, CETP, HL and LPL activities.
METHODS AND RESULTS: Rats were made hyperlipidemic by i.p. injection of 1.0 g/kg P-407 and blood samples collected 24 h after administration of P-407. Plasma from P-407-treated rats demonstrated 7- and 13-fold increases in cholesterol and triglycerides, respectively (p < 0.001). The plasma lecithin cholesterol acyl transferase (LCAT) activity in these animals was 4-5-fold greater than control animals (p < 0.05). Further, the plasma cholesteryl ester transfer protein (CETP) activity in P-407-treated rats was increased by approximately 25%, which was inhibited by > 50% in the presence of TP2, a monoclonal anti-CETP antibody (27.03 +/- 3.16 vs. 10.87 +/- 3.23; p < 0.05). The plasma CETP protein levels were also increased by 5-6-fold in P-407-treated animals (control 0.35 +/- 0.17 vs. P-407 treated 1.87 +/- 0.35 ug/ml, p < 0.05). However, the plasma hepatic lipase (HL) (control 49.2 +/- 3.1 vs. P-407-treated 2.0 +/- 0.38 umol/ml/h; p < 0.001) and lipoprotein lipase (LPL) (control 45.9 +/- 0.09 vs. P-407-treated 2.03 +/- 0.38 mol/ml/hr; p<0.001) activities in these animals were significantly inhibited.
CONCLUSIONS: In summary, P-407-induced hyperlipidemia in rats is associated with alterations in plasma LCAT, CETP, HL and LPL activities.