Mini meta-analysis of anticholinesterase actions of atorvastatin, simvastatin and rosuvastatin, and in silico identification of their protein targets in Mus musculus

Abstract

Dyslipidemic statins reduce blood and brain cholinesterase (ChE) activities in mice, with scarce information on other protein/enzyme targets. The study aims at conducting a mini meta-analysis on in vivo and in vitro adverse anti-ChE effects of atorvastatin, simvastatin and rosuvastatin in mice, and using the SwissPrediction to identify in silico body target proteins. The data comprised 72 records of plasma, erythrocytes and brain ChE activities, expressed as percent mean ± SD of respective controls. We conducted a randomized effects size single-arm meta-analysis. The risk of bias scoring was according to those of animal experiments. The effect size (% ChE activity) of statin treatments was significantly decreased by 25.85 % (combined effect size=74.15, p = 0.0001), with significant heterogeneity (Q=1133.19, p < 0.0001, I²=93.73 %). Subgroup analysis was significantly dose and concentration-dependent. The funnel plot showed non-symmetrical data distribution, with no imputed points. The risk of bias was moderate. In silico mouse body protein targets for the statins were mainly classes of Family AG protein- coupled receptor (20.0 %-33.3 %), Oxidoreductase (6.7–13.3 %) and Eraser (13.3 % each), with others at 0–26.7 %. The findings highlight statin effects in mice by reducing blood and brain ChE activities, in a dose/concentration-dependent manner, that would potentially modulate the cholinergic system. This anti-ChE effect together with in silico protein targets recognized could be the basis of further experimental explorations of adverse effects of statins.