Assessing plasma lipid levels, body weight, and hepatic and renal toxicityfollowing 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 in corporated into the diet or drinking water on plasma lipids, body weight, a nd hepatic and renal function following chronic oral administration to gerb ils. 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 moni tored weekly. Following 8 weeks of this regiment blood was obtained via a c ardiac puncture and all animals were sacrificed humanely. Plasma obtained f rom this blood was analyzed for total cholesterol, total triglyceride and h igh-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 fo r changes in hepatic enzyme (aspartate aminotransferase [AST] and alanine a minotransferase [ALT]) and plasma creatinine (renal function) concentration s. 2% and 4% FM-VP4 administration incorporated both into the diet and in t he drinking water resulted in a significant decrease in total plasma choles terol and LDL cholesterol concentration compared to controls. Animals admin istered 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 t reatment 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 d iet and drinking water groups compared to controls. A significant decrease in total plasma triglyceride concentration was observed in gerbils administ ered 4% FM-VP4 in their drinking water compared to controls. A significant increase in HDL cholesterol concentrations was observed in gerbils administ ered 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 concentr ations were reported for all treatment groups compared to controls. These f indings suggest that FM-VP4 significantly decrease plasma lipids and body w eight with no apparent hepatic or renal toxicity.