Effects of a novel hydrophilic phytostanol analog on plasma lipid concentrations in gerbils.
This study was designed to determine the effects of a novel hydrophilic phytostanol analog, FM-VP4, on total plasma cholesterol, total plasma triglyceride, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol concentrations after acute oral administration to gerbils. Gerbils were administered a standard gerbil diet for 4 continuous weeks, and daily water and food intake was monitored and replaced. The diet contained either no FM-VP4 (control) or FM-VP4 at the following concentrations: 0.25, 0.50, 1.0, or 2.0% w/w; six gerbils were fed each diet formulation. After 4 weeks of receiving a single diet formulation, blood was obtained from each gerbil by cardiac puncture and the animals were sacrificed humanely. Plasma obtained from this blood was analyzed for total cholesterol, total triglyceride, and HDL cholesterol levels by standard enzymatic and precipitation techniques. LDL cholesterol levels were calculated using the Friedewald equation. Administration of dietary FM-VP4 resulted in significant decreases in total plasma cholesterol and LDL cholesterol concentrations compared with controls. Dietary FM-VP4 at concentrations of 1% and 2% (w/w) decreased total plasma cholesterol by 3.4 mmol/L compared with controls. This decrease was entirely due to the loss of cholesterol from the LDL pool because LDL cholesterol was decreased by 3.3 and 3.2 mmol/L after 1% and 2% (w/w) FM-VP4, respectively. There were no significant changes in plasma triglyceride or HDL cholesterol concentrations after the administration of FM-VP4. Animals administered 1% or 2% (w/w) FM-VP4 also had significantly lower body weight after 4 weeks of treatment compared with the other groups. However, no unusual behavior was observed in these animals. No major differences in daily water or food intake were observed throughout the study. These findings indicate that FM-VP4 decreases total and LDL cholesterol concentrations.
Wasan
K M
KM
Division of Pharmaceutics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada V6E 3X2. kwasan@interchange.ubc.ca
Najafi
S
S
Peteherych
K D
KD
Pritchard
P H
PH
D000818:Animals; D000924:Anticholesteremic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004326:Drinking / Q000187:drug effects / Q000502:physiology; D004435:Eating / Q000187:drug effects / Q000502:physiology; D005849:Gerbillinae; D008055:Lipids / Q000097:blood*; D008297:Male; D010840:Phytosterols / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology
D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; C445524:FM-VP4 compound; D008055:Lipids; D010840:Phytosterols; D002784:Cholesterol