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Effects of Nicotinic Acid on Poloxamer 407‐Induced Hyperlipidemia
Author(s) -
Nash Virginia J.,
Johnston Thomas P.,
Palmer Warren K.
Publication year - 1996
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/j.1875-9114.1996.tb02912.x
Subject(s) - triglyceride , nicotinic agonist , hyperlipidemia , chemistry , hypertriglyceridemia , saline , cholesterol , medicine , endocrinology , poloxamer 407 , fatty acid , pharmacology , poloxamer , biochemistry , diabetes mellitus , receptor , organic chemistry , copolymer , polymer
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.