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Silicon is the element very similar to carbon, and bioactive siliconized compounds have therefore received much attention. Siliconization of a compound enhances its biological activities. In the present study the hypolipidemic effect and toxicity of clofibrate and its siliconized analog, silafibrate, were compared. The experiments were performed in hypercholesterolemicWistar rats. Animals received high fat diet with 62.75% normal chow, 2% cholesterol, 0.25% cholic acid, 15% lard oil, 10% wheat flour and 10% sucrose.Silafibrate(40 mg/kg/day) produced a predominant reduction in the serum levels of total cholesterol (28.4%, p < 0.001), triglycerides (62%, p < 0.0001) and low-density lipoproteins (27%, p < 0.001) being more effective than the reference drug clofibrate (20%, 40%, 14.5%; p < 0.05). Similarly, it increased the total antioxidant levels in serum by 40% (p < 0.05). Simultaneously, treatment with silafibrate also reduced the malondialdehyde(MDA) concentration by 41% (p < 0.05). LD50 of silafibrate, given orally,was greater than 2000 mg/kg body weight inalbino mice while LD50 for clofibrate was calculated to be 1220 mg/kg. Thirty-day subacute toxicity was also evaluated with oral daily dose at 25, 50 and 100 mg/kg body weight in Wistarrats. No significant changes in body weight, food intake, behavior, mortality, hematology, blood biochemistry, vital organ weight were detected. The results of this study indicate that the effectiveness and safety of thehypolipidemic drug, clofibrate, were enhanced remarkably by replacing chlorine atom in its phenoxy ring with trimethylsilyl.

Biological Evaluation of a Siliconized Analog of Clofibrate (Silafibrate) in Rodents