Clinical Study on the Effect of Simvastatin on Butyrylcholinesterase Activity

Abstract

Summary Although the physiological function of serum butyrylcholinesterase (BuChE) has not yet been clarified, there is evidence that this enzyme is involved in serum lipoprotein metabolism. It has been suggested that serum BuChE is positively correlated with LDL (low-density lipoprotein) and negatively with HDL (high-density lipoprotein) levels. The objective of this study was to determine whether the activity of BuChE changes during treatment with simvastatin (CAS 79902-63-9). The effects of simvastatin therapy on serum lipoproteins and plasma BuChE activity were studied in 15 patients with type IIa and 17 patients with type IIb hyperlipoproteinemia. Beside the expected influence on serum lipid concentration, a statistically significant decrease in BuChE activity in patients with hyperli-poproteinemia type IIa and IIb during treatment with simvastatin was not observed.

Differential effects of statins on plasma and brain cholinesterase activities in chicks

“…Based on the present results regarding the effects of statins on ChE activity following drug type and duration of therapy as well as on the results of other investigators (Darvesh et al, 2004;Cibickova et al, 2007;Roensch et al, 2007;Vukšić et al, 2019), caution should be practised in generalising this notion on all statins, which differ considerably in their pharmacokinetic, pharmacodynamics, and even neurotoxic profiles (Bocan, 2002;Butterfield et al, 2011;Zhang et al, 2018;Hirota et al, 2020). The statins vary greatly when pseudo and true ChE are considered for any activity modulation (Zdrenghea et al, 2002;Darvesh et al, 2004;Muačević-Katanec et al, 2005;Cibickova et al, 2007;Cibickova et al, 2009;Macan et al, 2015;Vukšić et al, 2019). Therefore, extensive preclinical studies are needed on different types of statins, considering their anti-ChE and potential neurotoxic effects.…”

“…Lovastatin and simvastatin inhibited plasma ChE activity, whereas mevastatin and pravastatin did not in patients on lipidlowering therapy (Darvesh et al, 2004). Moreover, patients on simvastatin did not suffer from changes in serum ChE (Zdrenghea et al, 2002;Muačević-Katanec et al, 2005). Based on these studies, current evidence suggests no single unified pharmacological effect of statins on blood or brain ChE activity, as the statins vary in their chemical and physical properties and pharmacological effects (Bocan, 2002;Zhang et al, 2018;Hirota et al, 2020;Fan et al, 2021).…”

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

“…It is known for a fact that rodents are more susceptible to peroxisome proliferators than dogs, rhesus monkeys, or humans. Probably this difference in PPARα receptor sensitivity to statins and fibrates is the reason why statins either do not affect or lower plasma enzyme activity in humans (4,21,43).…”

“…Fibrates have also been shown to increase BuChE activity in non-clinical studies (19,20). Clinical evidence, in turn, is still not strong enough to reach definitive conclusions about the effects of lipid-lowering agents on plasma BuChE activity (4,21).…”

Effects of simvastatin on malondialdehyde level and esterase activity in plasma and tissue of normolipidemic rats

“…Statins may also modulate the activity of two serum esterases, paraoxonase 1 (PON1) [7] and butyrylcholinesterase (BuChE) [8], with unknown physiological function at present. Both enzymes are synthesized in the liver and hypothetically are involved in metabolism of lipids.…”