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

Abstract

ObjectivesThe goal of the present study was to evaluate the effects of D-003 (5 to 200 mg/kg) 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. BackgroundD-003 is a mixture of higher primary aliphatic acids; octacosanoic acid is its major component. MethodsThirty-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 mg/kg). ResultsAfter 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< 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 with-drawal. No rebound effects were observed. In addition, drug-related toxicity regarding mortality, food consumption, weight gain, or blood chemistry safety indicators was not evident. ConclusionsResults 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.