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

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 s ame source with experimentally proven cholesterol-lowering effects. Objective: The present study was undertaken to compare the cholesterol-lowe ring effects of D-003 and policosanol in normocholesterolemic New Zealand r abbits. In addition, the effects of the 2 drugs on levels of plasma circula ting endothelial cells (PCEC) before and after citrate-induced endothelial damage were compared. Methods: Animals were randomly distributed to 3 experimental groups: 1 cont rol and 2 treatment groups. Rabbits in the treatment groups received orally administered policosanol or D-003 daily at 5 mg/kg, the lowest effective d ose of policosanol in this model, for 30 days. Results: After 15 days of treatment, both D-003 and policosanol significant ly (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-den sity 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 comp ared with the control group, and LDL-C reductions were significantly greate r (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 int erim assessment. After 30 days, the reductions in LDL-C and TC were enhance d in both groups, with the percentage reductions in LDL-C significantly gre ater (P < 0.05) in the D-003 group (81.6%) than in the policosanol group (6 8.7%). Percent changes in TC were similar in both treatment groups-D-003 (4 2.4%) and policosanol (41.2%), although final values of TC in the D-003 gro up were significantly lower (P < 0.05) than in the policosanol group. Both drugs significantly raised high-density lipoprotein cholesterol (HDL-C) lev els versus baseline (P < 0.05), but the percent increases in the D-003 grou p (78.8%) were larger than in the policosanol group (47.1%). Serum triglyce ride levels did not change significantly in either treatment group. No sign ificant changes in lipid profile were observed in the control group. The PC EC count at study completion before and after citrate-induced endothelial d amage was significantly lower (P<0.001) in the treatment groups than in the control group, but was statistically similar between treatment groups. How ever, 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 normochole sterolemic rabbits induced more beneficial changes in serum LDL-C levels th an 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 policosa nol. Although D-003 was more effective than policosanol in these experiment al conditions, additional comparative studies that include a wide dose rang e of both drugs must be conducted before definitive conclusions can be made about the comparative cholesterol-lowering effects of D-003.