Nitrogen-containing bisphosphonates were found to inhibit farnesyl diphosphate synthase - an essential enzyme in the cholesterol biosynthesis pathway, but their effect on cholesterol synthesis per se in the central nervous system (CNS) remains unknown. The aim of the present study was to examine possible influence of a representative agent alendronate on cholesterol synthesis rates in selected parts of rat CNS and on plasma cholesterol level. Two groups of rats were orally administered either alendronate (3 mg/kg b.w. ) or vehicle for 9 days. At the end of experiment, brain (basal ganglia, frontal cortex and hippocampus) and spinal cord were isolated and cholesterol synthesis was determined using the technique of deuterium incorporation from deuterated wa ter. In the alendronate group significant reductions of choleste rol synthesis rates were detected in frontal cortex, hippocampus and spinal cord (p<0.001). However, the experimental treatment did not produce a significant alteration in the levels of plasma cholesterol. In conclusion, this study brings the first experimental evidence of the inhibition of cholesterol biosynthesis with alendronate in central nervous system., Ľ. Cibičková, R. Hyšpler, N. Cibiček, E. Čermáková, V. Palička., and Obsahuje bibliografii
Acetylcholinesterase (AChE) inhibitors represent standard treatment of Alzheimer´s disease. Cholesterol plays an important role in Alzheimer´s disease development. Because cholesterol synthesis may be inhibited by statins or bisphosphonates, we hypothesized that these drugs might possibly have an influence on cholinesterases. Moreover, we also evaluated if the cholesterol-lowering agents that cross the blood-brain barrier (e.g. simvastatin) should be more effective than those which do not (e.g. atorvastatin). Four groups of rats were orally administered simvastatin, atorvastatin, alendronate or vehicle for seven days. Thereafter, blood samples were taken and the basal ganglia, septum, frontal cortex, and hippocampus were isolated from brains for measurement of acetylcholinesterase activity. In the blood, activities of neither acetyl- nor butyrylcholinesterase were influenced by any of the applied drugs. In the brain, no significant changes in AChE activity were observed after administration of atorvastatin. Both simvastatin and alendronate significantly suppressed the activity of AChE in the frontal cortex. In conclusion, our results confirmed the hypothesis that cholesterol-modifying drugs modulate AChE activity and it is more reasonable to use a blood-brain barrier penetrating drug., Ľ. Cibičková, V. Palička, N. Cibiček, E. Čermáková, S. Mičuda, L. Bartošová, D. Jun., and Obsahuje bibliografii a bibliografické odkazy