Opposite effects of bezafibrate and gemfibrozil in both normal and hypertriglyceridemic rats

Atherosclerosis
B R KrauseC L Bisgaier

Abstract

Chow and sucrose-fed rats were used as animal models to study the dose-responses of bezafibrate and gemfibrozil in normolipidemic and hypertriglyceridemic states, respectively. Although both drugs lowered plasma triglycerides (TG) to about the same extent in chow-fed rats, gemfibrozil lowered liver TG as well as plasma total and LDL-cholesterol (LDL-C), but elevated HDL-cholesterol (HDL-C) and plasma apo E concentrations. Bezafibrate produced opposite effects, namely, decreased HDL-C, apo E and liver TG, and tended to increase LDL-C. TG lowering for both drugs in chow-fed rats was not due to changes in TG secretion (production) in normal rats but was associated with enhanced LPL activity. In hypertriglyceridemic rats both drugs modestly reduced TG secretion rates about 40% at a dose producing maximal TG lowering, but again, gemfibrozil elevated and bezafibrate lowered HDL-C and apo E. Unlike gemfibrozil, bezafibrate induced the appearance of LDL-C in hypertriglyceridemic rats which was not detected in control animals, and also tended to increase rather than decrease plasma apo B levels. Finally, changes in liver TG concentration (mg/g) in hypertriglyceridemic rats were opposite for these drugs, resulting in significant drug-rel...Continue Reading

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Citations

Oct 27, 1998·Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology·K NagaoK Imaizumi
Jan 13, 2000·Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology·K NagaoK Imaizumi
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Oct 6, 2009·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Xuemei FangJiayin Dai

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