Effects of nicotinic acid on poloxamer 407-induced hyperlipidemia.
We attempted to determine the mechanism(s) of poloxamer (P)-407-induced hyperlipidemia in rats by administering a lipid-lowering drug with a known mechanism of action. Five weight-matched animals were assigned to each of four treatment groups. Two groups received P-407 300 mg/ml and two received saline 1 ml. One of the P-407 and one of the saline groups were administered nicotinic acid 100 mg/kg by intraperitoneal injection at 6-96 hours after blood sampling. Blood samples were collected at 7 points from time zero to 120 hours and analyzed for triglyceride and cholesterol concentrations. The detergent produces hypertriglyceridemia (HTG) increasing from 53.4 +/- 7.0 mg/dl (time zero) to 4026.9 +/- 42.1 mg/dl by 24 hours. The HTG response was significantly attenuated by nicotinic acid (at t = 24 hrs). This, however, was followed by an average triglyceride concentration increase of 2.8-fold from 72 to 120 hours. The detergent produces a dramatic hypercholesterolemia (HCHO), increasing cholesterol from 47.5 +/- 1.8 mg/dl to 468.5 +/- 27.9 mg/dl by 48 hours. The HCHO was significantly affected by nicotinic acid administration during the accumulation phase. Nicotinic acid reduced cholesterol concentration from 364.4 +/- 16.1 mg/dl to 276.8 +/- 16.4 mg/dl at 24 hours (p < 0.05). It is a potent antilipolytic agent, limiting the free fatty acids available for the synthesis of triglyceride and cholesterol. These data suggest that P-407 may act by stimulating the release of free fatty acids from the adipocyte for at least 24 hours after injection.
Nash
V J
VJ
School of Kinesiology, University of Illinois at Chicago 60608, USA.
Johnston
T P
TP
Palmer
W K
WK
D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight; D004338:Drug Combinations; D005215:Fasting; D006949:Hyperlipidemias / Q000097:blood / Q000139:chemically induced* / Q000517:prevention & control; D007274:Injections, Intraperitoneal; D008297:Male; D009525:Niacin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D011060:Poloxalene / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013501:Surface-Active Agents / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
D004338:Drug Combinations; D013501:Surface-Active Agents; D014280:Triglycerides; D009525:Niacin; D011060:Poloxalene