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Alendronate lowers cholesterol synthesis in the central nervous system of rats - a preliminary study
L Cibickova1, R Hyspler, N Cibicek
1Second Department of Medicine, University Hospital, Hradec Králové, Czech Republic. cibickova@seznam.cz
Abstract:
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 water. In the alendronate group significant reductions of cholesterol 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.
Insights
Alendronate, a bisphosphonate, significantly reduces cholesterol synthesis in the rat central nervous system (CNS). However, it does not affect plasma cholesterol levels, indicating a specific CNS impact.
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- Nitrogen-containing bisphosphonates inhibit farnesyl diphosphate synthase.
- The impact of these drugs on central nervous system (CNS) cholesterol synthesis is unknown.
Purpose of the Study:
- To investigate the effect of alendronate on cholesterol synthesis rates in specific rat CNS regions.
- To assess alendronate's influence on plasma cholesterol levels.
Main Methods:
- Rats were administered alendronate or vehicle orally for 9 days.
- Cholesterol synthesis was measured in brain regions (basal ganglia, frontal cortex, hippocampus) and spinal cord using deuterium incorporation.
- Plasma cholesterol levels were also analyzed.
Main Results:
- Alendronate significantly reduced cholesterol synthesis rates in the frontal cortex, hippocampus, and spinal cord (p<0.001).
- No significant alteration in plasma cholesterol levels was observed in the alendronate-treated group.
Conclusions:
- This study provides the first experimental evidence that alendronate inhibits cholesterol biosynthesis within the CNS.
- Alendronate demonstrates a specific inhibitory effect on CNS cholesterol synthesis, independent of plasma cholesterol levels.
