Mini meta-analysis of anticholinesterase actions of atorvastatin, simvastatin and rosuvastatin, and in silico identification of their protein targets in Mus musculus
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...
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Elsevier
2025-06-01
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| author | Fouad Kasim Mohammad Rawnaq Faris Al-Shalchi |
| author_facet | Fouad Kasim Mohammad Rawnaq Faris Al-Shalchi |
| author_sort | Fouad Kasim Mohammad |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-b8467b634f49404db47290fe8627cbec |
| institution | Kabale University |
| issn | 2214-7500 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Toxicology Reports |
| spelling | doaj-art-b8467b634f49404db47290fe8627cbec2025-02-12T05:31:09ZengElsevierToxicology Reports2214-75002025-06-0114101958Mini meta-analysis of anticholinesterase actions of atorvastatin, simvastatin and rosuvastatin, and in silico identification of their protein targets in Mus musculusFouad Kasim Mohammad0Rawnaq Faris Al-Shalchi1Department of Physiology, Biochemistry and Pharmacology, College of Veterinary Medicine, University of Mosul, Mosul, Iraq; College of Nursing, The American University of Kurdistan, Duhok, Iraq; Corresponding author at: Department of Physiology, Biochemistry and Pharmacology, College of Veterinary Medicine, University of Mosul, Mosul, Iraq.Department of Physiology, Biochemistry and Pharmacology, College of Veterinary Medicine, University of Mosul, Mosul, IraqDyslipidemic 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.http://www.sciencedirect.com/science/article/pii/S2214750025000769StatinsDyslipidemiaCholinesteraseProtein targetsMice |
| spellingShingle | Fouad Kasim Mohammad Rawnaq Faris Al-Shalchi Mini meta-analysis of anticholinesterase actions of atorvastatin, simvastatin and rosuvastatin, and in silico identification of their protein targets in Mus musculus Toxicology Reports Statins Dyslipidemia Cholinesterase Protein targets Mice |
| title | Mini meta-analysis of anticholinesterase actions of atorvastatin, simvastatin and rosuvastatin, and in silico identification of their protein targets in Mus musculus |
| title_full | Mini meta-analysis of anticholinesterase actions of atorvastatin, simvastatin and rosuvastatin, and in silico identification of their protein targets in Mus musculus |
| title_fullStr | Mini meta-analysis of anticholinesterase actions of atorvastatin, simvastatin and rosuvastatin, and in silico identification of their protein targets in Mus musculus |
| title_full_unstemmed | Mini meta-analysis of anticholinesterase actions of atorvastatin, simvastatin and rosuvastatin, and in silico identification of their protein targets in Mus musculus |
| title_short | Mini meta-analysis of anticholinesterase actions of atorvastatin, simvastatin and rosuvastatin, and in silico identification of their protein targets in Mus musculus |
| title_sort | mini meta analysis of anticholinesterase actions of atorvastatin simvastatin and rosuvastatin and in silico identification of their protein targets in mus musculus |
| topic | Statins Dyslipidemia Cholinesterase Protein targets Mice |
| url | http://www.sciencedirect.com/science/article/pii/S2214750025000769 |
| work_keys_str_mv | AT fouadkasimmohammad minimetaanalysisofanticholinesteraseactionsofatorvastatinsimvastatinandrosuvastatinandinsilicoidentificationoftheirproteintargetsinmusmusculus AT rawnaqfarisalshalchi minimetaanalysisofanticholinesteraseactionsofatorvastatinsimvastatinandrosuvastatinandinsilicoidentificationoftheirproteintargetsinmusmusculus |