Dose-dependent cholesterol-lowering effects of D-003 on normocholesterolemic rabbits

Abstract

Objectives: The goal of the present study was to evaluate the effects of D-003 (5 to 200 mgkg) administered orally for 30 days on the serum lipid profile of normocholesterolemic New Zealand rabbits as well as the effects of treatment withdrawal for the following 30 days. Background: D-003 is a mixture of higher primary aliphatic acids; octacosanoic acid is its major component. Methods: Thirty-five animals were adapted to experimental conditions for 15 days and then randomized to 5 study groups: a control group, which received only orally equivalent volumes of the vehicle, and 4 groups treated with the various doses of D-003 (5, 25, 100, or 200 mgkg). Results: After 30 days of treatment, D-003 significantly (P < 0.01) and dose-dependently reduced levels of both total cholesterol (TC) (range, 27.5% to 37.3%) and low-density lipoprotein cholesterol (LDL-C) (range, 64.5% to 84.4%). After 30 days of treatment, high-density lipoprotein cholesterol (HDL-C) levels increased in all treated groups compared with baseline. Only the final values of the groups receiving doses of 25 to 200 mg/kg were significantly larger (P c 0.01) than those of the control group. This effect was not dose dependent. No drug-related effects on triglycerides were noted. There were no significant changes in the control group’s lipid profile during the study. The effects of D-003 on TC, LDL-C, and HDL-C levels were reversible after the washout period, with complete recovery to baseline values after 30 days of treatment withdrawal. No rebound effects were observed. In addition, drug-related toxicity regarding mortality, food consumption, weight gain, or blood chemistry safety indicators was not evident. Conclusions: Results of this study suggest that D-003 has reversible cholesterol-lowering effects characterized by a dosedependent reduction of TC and LDL-C values accompanied by a non-dose-dependent increase in HDL-C levels.