Assessing plasma lipid levels, body weight, and hepatic and renal toxicity following chronic oral administration of a water soluble phytostanol compound, FM-VP4, to gerbils.
The purpose of this project was to determine the effect of a FM-VP4 when incorporated into the diet or drinking water on plasma lipids, body weight, and hepatic and renal function following chronic oral administration to gerbils. Gerbils were administered water and food daily containing either no FM-VP4 (controls; n=6), 2% or 4% FM-VP4 incorporated into the gerbil diet (n=6 each treatment group) or 2% or 4% FM-VP4 dissolved in the drinking water (n=6 each treatment group). Body weight and food and water intake were monitored weekly. Following 8 weeks of this regiment blood was obtained via a cardiac puncture and all animals were sacrificed humanely. Plasma obtained from this blood was analyzed for total cholesterol, total triglyceride and high-density lipoprotein (HDL)-cholesterol levels by standard enzymatic and precipitation techniques. Low-density lipoprotein (LDL)-cholesterol levels were determined by the Friedewald equation. The plasma was also analyzed for changes in hepatic enzyme (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) and plasma creatinine (renal function) concentrations. 2% and 4% FM-VP4 administration incorporated both into the diet and in the drinking water resulted in a significant decrease in total plasma cholesterol and LDL cholesterol concentration compared to controls. Animals administered 4% FM-VP4 in either their diet or drinking water had significantly lower body weight following the 8 weeks of treatment compared to the other groups. Significant differences in daily water intake was observed in all treatment groups with the exception of the 2% FM-VP4 in diet group compared to controls. Significant differences in daily food intake were observed in gerbils administered 2% FM-VP4 in the drinking water and 4% FM-VP4 in the diet and drinking water groups compared to controls. A significant decrease in total plasma triglyceride concentration was observed in gerbils administered 4% FM-VP4 in their drinking water compared to controls. A significant increase in HDL cholesterol concentrations was observed in gerbils administered 2% FM-VP4 in their diet and 4% FM-VP4 in their drinking water compared to controls. No significant elevations in AST, ALT and creatinine concentrations were reported for all treatment groups compared to controls. These findings suggest that FM-VP4 significantly decrease plasma lipids and body weight with no apparent hepatic or renal toxicity.
Wasan
K M
KM
Division of Pharmaceutics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada. kwasan@interchange.ubc.ca
Najafi
S
S
Wong
J
J
Kwong
M
M
Pritchard
P H
PH
D000284:Administration, Oral; D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects*; D056486:Chemical and Drug Induced Liver Injury; D008078:Cholesterol, LDL / Q000097:blood; D005849:Gerbillinae; D007668:Kidney / Q000187:drug effects; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced*; D008055:Lipids / Q000097:blood*; D008099:Liver / Q000187:drug effects; D008107:Liver Diseases / Q000097:blood; D010840:Phytosterols / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology*; D012995:Solubility; D014867:Water / Q000378:metabolism*
D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; C445524:FM-VP4 compound; D008055:Lipids; D010840:Phytosterols; D014867:Water