Abstract
The effect of the hypolipidemic agent AJ814, a derivative of azunole, on lipid metabolism in rabbits was investigated. In experiment 1, the results of weekly body weight measurements showed no significant differences between the two groups. There also was no significant differences in food intake between the two groups. The effect of AJ814 (3mg/100mg body weight) on lipid metabolism in 0.1% cholesterol-fed white Japanese rabbits was observed over 12 weeks. The mean total serum cholesterol (TC) in the drug-treated group was 57.6% of the controls after 8 weeks treatment. Moreover, the mean value for the area of the aorta with atherosclerotic plaque in the drugtreated group was only 12.3% of the controls (p<0.05). The mean incidence of coronary arteries with intimal thickening in the treated group was 35.6% of the controls (p<0.01). The serum triglyceride (TG), phospholipid (PL) and lipid peroxide (LPO) also decreased compared with those in controls. In Exp. 2, the effect of AJ814 (6mg/100mg body weight) on serum lipids in white rabbits injected with Triton WR-1339 was followed for 120 hours after injection. In Exp. 3, the effect of AJ814 (6mg/100g body weight) on serum lipids in WHHL rabbits was followed for 16 days after the drug was administered. In Exps. 2 and 3, the serum TC, HDL-C, TG and PL of drugtreated rabbits showed no significant differences when compared with controls. Based on these results, the mechanism of the lipid-lowering effect of AJ814 in cholesterol-fed rabbits appears to be based on inhibition of lipid absorption from the intestine.
