Effects of F2833 on cholesterol metabolism in the genetically hyperlipidemic rat.

摘要

The effects of the new hypolipidemic agent, F2833 or (chloro 2' (1-1') biphenyl-4)-2 propanol-2, on cholesterol metabolism were studied in genetically hyperlipidemic rats (RICO). Cholesterolemia decreased after 2 days of treatment to 60% of its initial value (1.20+/-0.10 g/l vs. 1.99+/-0.08, P < 0.001) and then stabilised within 10 days. This hypocholesterolemic action was effective for as long as 3 months. Concerning the different classes of lipoproteins, a significant drop was observed in HDL (high density lipoproteins) (25%, 0.49 +/- 0.02 g/l vs. 0.66 +/- 0.007, P < 0.01) and particularly in LDL (low density lipoproteins) (70%, 0.30 +/- 0.04 g/l vs. 0.92 +/- 0.05, P < 0.001). Whole body cholesterol showed a higher fractional catabolic rate (0.25 +/- 0.02 vs. 0.17 +/- 0.005 day(-1), P < 0.01) together with an increased cholesterol synthesis (60 +/- 5 vs. 36 +/- 4 mg/day, P < 0.01). LDL kinetics showed that the decrease in these lipoproteins is essentially caused by an increase in the fractional catabolic rate (10.6 +/-0.1%/h vs. 5.2 +/- 0.1%/h, P < 0.001) and by a lesser decrease in the LDL production rate. This cholesterol metabolic profile created by treatment suggests an effect through stimulation of cholesterol output (biliary cholesterol elimination or cholesterol transformation into bile acids).