In vivo Hypocholesterolemic Investigation of Synthetic Cholesterol Congeners

The elevation of plasma cholesterol and lipoproteins are well-documented risk factors as development of atherosclerosis. The reduction of plasma cholesterol by dietary and/or pharmacological means leads to reductions in the incidence of death from cardiovascular disease. These facts motivated and inspired the discovery of anti hypercholesterolemic drugs such as cholesterol absorption inhibitors (ezetimibe) and hepatic cholesterol biosynthesis inhibitors (statins). The aim of study is to investigate in vivo hypocholesterolemic, toxicity and related metabolic effects of a set of five synthetic cholesterol congeners Glu-Chol (2), Azid-Chol (3), Bi-Chol (4), Fer-3-Chol (5) and Azo-Chol (11) of divergent structures on high-cholesterol-diet feed male SD mice. To achieve this objective, serum total cholesterol (TC), triglycerides (TG), highdensity lipoprotein (HDL), and fasting blood glucose (FBG), liver function parameters like serum glutamate-pyruvate transaminase (GPT), glutamic oxaloacetic transaminase (GOT), kidney function parameters like creatinine and urea levels were assayed using auto analyzer A15 (Biosystem, Barcelona, Spain. Moreover, histopathological Investigations of liver, kidney and heart tissues was performed. Results indicated that compound 2 has concurrent little attenuation in cholesterol. Compound 3 has lethal effect of the mice. Compound 4 led to increase in cholesterol levels. Compound 5, despite it decreased serum cholesterol levels, it led to toxic effects. The azodye conjugate (11) dimensioned the cholesterol levels a little but has negative effect of mice activities. It is concluded that the synthetic cholesterol congeners have hypocholesterolemic and it seems that negative effects on the animals with the ferrocene derivative 5 might be further considered as rodenticide rather than being considered as hypocholesterolemic agent. Advanced investigations to prove its mechanism of action using various doses is highly recommended.