Effects of simvastatin and fenofibrate on butyrylcholinesterase activity in the brain, plasma, and liver of normolipidemic and hyperlipidemic rats

The study objective was to test the hypothesis that simvastatin and fenofibrate should cause an increase in butyrylcholinesterase (BuChE) activity not only in the plasma and liver but also in the brain of normolipidemic and hyperlipidemic rats. Catalytic enzyme activity was measured using acetylthiocholine (ATCh) and butyrylthiocholine (BTCh) as substrates. Normolipidemic and hyperlipidemic rats were divided in four groups receiving 50 mg/kg of simvastatin a day or 30 mg/kg of fenofibrate a day for three weeks and three control groups receiving saline. Simvastatin and fenofibrate caused an increase in brain BuChE activity in both normo- and hyperlipidemic rats regardless of the substrate. The increase with BTCh as substrate was significant and practically the same in normolipidemic and hyperlipidemic rats after simvastatin treatment (14–17% vs controls). Simvastatin and fenofibrate also increased liver and plasma BuChE activity in both normolipidemic and hyperlipidemic rats regardless of the substrate. In most cases the increase was significant. Considering the important role of BuChE in cholinergic transmission as well as its pharmacological function, it is necessary to continue investigations of the effects of lipid-lowering drugs on BuChE activity.
Cilj ispitivanja bio je u normolipidemičnih i hiperlipidemičnih štakora potvrditi pretpostavku da simvastatin (SIMV) I fenofibrat (FENO) ne uzrokuju samo povećanje aktivnosti butirilkolinesteraze (BuChE) u plazmi i jetri nego i povećavaju aktivnosti BuChE u mozgu. Katalitička aktivnost enzima mjerena je upotrebom acetiltiokolina (ATCh) i butiriltiokolina (BTCh) kao supstrata. Normolipidemični i hiperlipidemični štakori raspoređeni su u eksperimentalne skupine, koje su tri tjedna primale SIMV 50 mg/kg na dan ili FENO 30 mg/kg na dan, dok su kontrolne skupine primale fiziološku otopinu. I SIMV i FENO uglavnom su izazvali povećanje aktivnosti BuChE u mozgu obaju sojeva štakora bez obzira na korišteni supstrat. Aktivnosti BuChE mjerene BTCh kao supstratom bile su značajno veće u odnosu na kontrolne vrijednosti u mozgu normolipidemičih štakora nakon primjene SIMV te u mozgu hiperlipidemičnih štakora nakon primjene obaju agensa (14‒17%, p<0,001). Povećanje aktivnosti BuChE u plazmi i jetri nakon primjene SIMV i FENO izmjeren je u oba soja štakora bez obzira na to je li korišten ACTh ili BTCh. U većini slučajeva povećanje aktivnosti BuChE u plazmi i jetri bilo je značajno. S obzirom na važnu ulogu BuChE u kolinergičnom prijenosu te na njezinu farmakološku funkciju, potrebno je nastaviti istraživanja utjecaja antilipidnih lijekova na aktivnost BuChE.