Comparison of the effects of D-003 and policosanol on lipid profile and endothelial cells in normocholesterolemic rabbits

Abstract

Background: Policosanol is a cholesterol-lowering drug purified from sugar cane wax that consists of a mixture of higher aliphatic primary alcohols. D-003 is a mixture of long-chain aliphatic primary acids isolated from the same source with experimentally proven cholesterol-lowering effects. Objective: The present study was undertaken to compare the cholesterol-lowering effects of D-003 and policosanol in normocholesterolemic New Zealand rabbits. In addition, the effects of the 2 drugs on levels of plasma circulating endothelial cells (PCEC) before and after citrate-induced endothelial damage were compared. Methods: Animals were randomly distributed to 3 experimental groups: 1 control and 2 treatment groups. Rabbits in the treatment groups received orally administered policosanol or D-003 daily at 5 mg/kg, the lowest effective dose of policosanol in this model, for 30 days. Results: After 15 days of treatment, both D-003 and policosanol significantly ( P < 0.05) lowered serum levels of total cholesterol (TC) compared with baseline, but only D-003 significantly reduced ( P < 0.05) levels of low-density lipoprotein cholesterol (LDL-C). At 15 days, the absolute values of TC and LDL-C were significantly lower ( P < 0.05) only in the D-003 group compared with the control group, and LDL-C reductions were significantly greater ( P < 0.05) in the D-003 group (45.3%) than in the policosanol group (38.1%). No other significant changes in lipid profile were observed at this interim assessment. After 30 days, the reductions in LDL-C and TC were enhanced in both groups, with the percentage reductions in LDL-C significantly greater ( P < 0.05) in the D-003 group (81.6%) than in the policosanol group (68.7%). Percent changes in TC were similar in both treatment groups—D-003 (42.4%) and policosanol (41.2%), although final values of TC in the D-003 group were significantly lower ( P < 0.05) than in the policosanol group. Both drugs significantly raised high-density lipoprotein cholesterol (HDL-C) levels versus baseline ( P < 0.05), but the percent increases in the D-003 group (78.8%) were larger than in the policosanol group (47.1%). Serum triglyceride levels did not change significantly in either treatment group. No significant changes in lipid profile were observed in the control group. The PCEC count at study completion before and after citrate-induced endothelial damage was significantly lower ( P < 0.001) in the treatment groups than in the control group, but was statistically similar between treatment groups. However, the increases in PCEC count after citrate-induced damage in the D-003 group was significantly ( P < 0.05) lower than in the other groups. Conclusions: D-003 administered orally at 5 mg/kg for 30 days to normocholesterolemic rabbits induced more beneficial changes in serum LDL-C levels than policosanol at the same dose. In addition, a slightly greater beneficial effect on HDL-C levels and PCEC count was noted with D-003 versus policosanol. Although D-003 was more effective than policosanol in these experimental conditions, additional comparative studies that include a wide dose range of both drugs must be conducted before definitive conclusions can be made about the comparative cholesterol-lowering effects of D-003.