Differential effects of statins and alendronate on cholinesterases in serum and brain of rats.
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.
Cibicková
L
L
Second Department of Medicine, University Hospital, Hradec Králové, Czech Republic. cibickoval@lfhk.cuni.cz
Palicka
V
V
Cibicek
N
N
Cermáková
E
E
Micuda
S
S
Bartosová
L
L
Jun
D
D
D019386:Alendronate / Q000494:pharmacology*; D000818:Animals; D000069059:Atorvastatin; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D002091:Butyrylcholinesterase / Q000097:blood; D002802:Cholinesterases / Q000097:blood / Q000378:metabolism*; D006538:Heptanoic Acids / Q000494:pharmacology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008297:Male; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D019821:Simvastatin / Q000494:pharmacology
D050071:Bone Density Conservation Agents; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin; D019821:Simvastatin; D002091:Butyrylcholinesterase; D002802:Cholinesterases; D019386:Alendronate