Poloxamer 407-mediated alterations in the activities of enzymes regulating lipid metabolism in rats

• Published in: Journal of pharmacy & pharmaceutical sciences Vol. 6; no. 2; p. 189
• Main Authors: Wasan, Kishor M, Subramanian, Ramaswamy, Kwong, Mona, Goldberg, Ira J, Wright, Thamrah, Johnston, Thomas P
• Format: Journal Article
• Language: English
• Published: Canada 01.05.2003
• Subjects: Animals; Carrier Proteins - metabolism; Cholesterol Ester Transfer Proteins; Excipients - adverse effects; Excipients - pharmacology; Glycoproteins; Hyperlipidemias - chemically induced; Hyperlipidemias - enzymology; Lipase - metabolism; Lipids - blood; Lipoprotein Lipase - metabolism; Male; Phosphatidylcholine-Sterol O-Acyltransferase - metabolism; Poloxamer - adverse effects; Poloxamer - pharmacology; Rats; Rats, Sprague-Dawley
• ISSN: 1482-1826

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. 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. In summary, P-407-induced hyperlipidemia in rats is associated with alterations in plasma LCAT, CETP, HL and LPL activities.