OPPOSITE EFFECTS OF BEZAFIBRATE AND GEMFIBROZIL IN BOTH NORMAL AND HYPERTRIGLYCERIDEMIC RATS

Chow and sucrose-fed rats were used as animal models to study the dose -responses of bezafibrate and gemfibrozil in normolipidemic and hypert riglyceridemic states, respectively. Although both drugs lowered plasm a triglycerides (TG) to about the same extent in chow-fed rats, gemfib rozil lowered liver TG as well as plasma total and LDL-cholesterol (LD L-C), but elevated HDL-cholesterol (HDL-C) and plasma apo E concentrat ions. 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 (produc tion) in normal rats but was associated with enhanced LPL activity. In hypertriglyceridemic rats both drugs modestly reduced TG secretion ra tes about 40% at a dose producing maximal TG lowering, but again, gemf ibrozil elevated and bezafibrate lowered HDL-C and apo E. Unlike gemfi brozil, bezafibrate induced the appearance of LDL-C in hypertriglyceri demic 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 op posite for these drugs, resulting in significant drug-related differen ces in liver TG content (mg/organ). From these data we postulate that, although similar with regard to TG lowering activity and mechanisms t hereof, gemfibrozil and bezafibrate produce fundamentally different ef fects on LDL, HDL and apolipoprotein metabolism (ape B and apo E) in r ats which may relate to potential differential effects on reverse chol esterol transport and atherogenesis.