Mini meta-analysis of anticholinesterase actions of atorvastatin, simvastatin and rosuvastatin and in silico identification of their protein targets in Mus musculus
Creators: name: Rawnaq F. Al-Shalchi
name: Mohammad, Fouad K.
Publisher: name: OSF Registries
Year: 2024
Subjects: subject: Medicine and Health Sciences
subject: Life Sciences
subject: Cholinesterase
subject: Hypolipidemic drugs
subject: Protein targets
subject: Statins

description: Dyslipidemic statins are widely used clinically to decrease serum cholesterol level by inhibiting the target enzyme 3-hydroxy-3-methylglutaryl-coenzyme A. In spite of the similarity in the clinical outcome of statins by reducing blood cholesterol, low density lipoproteins and triglyceride levels, they vary considerably in their pharmacokinetic, pharmacodynamics profiles and pleiotropic effects.

Adverse actions of statins mainly involve the liver and skeletal muscles paralleled with central effects. Several experimental animal studies highlight adverse effects of statins in an attempt to produce an animal model of statin intolerance. Statins affect neurobehavioral and cognitive functions and metabolomic changes in biological fluids, the blood and several organ systems in laboratory animals such as rats, mice and young chicks. Examples of metabolomic changes of statins include but not limited to reduced blood and brain cholinesterase (ChE) activities, oxidative stress by increasing blood and tissue malondialdehyde (MDA) levels and reducing glutathione (GSH) content, changes in liver enzymes activities indicating liver injury, circulating endocan as well as changes in amino acids levels.

Recently, we have attempted to describe undesirable/adverse effects of three statins (atorvastatin, simvastatin and rosuvastatin) following experimental single or repeated doses in mice. These effects are characterized by neurobehavioral alterations that included exploratory open-field depression, negative geotaxis performance, head pocking behavior and forced swimming endurance. In parallel with these effects specific biochemical alterations reported in statin-treated mice included inhibition of blood and brain ChE activities, increased MDA level, reduced GSH level and increased liver enzymes. Statins may target specific proteins such the ChE, cellular membranes or tissue redox oxidant/antioxidant systems. This projects involves conducting a mini meta-analysis on our won specific published data we reported in mice on the overall in vivo and in vitro adverse anti-ChE effects of statins (atorvastatin, simvastatin and rosuvastatin), comprising 72 records, as well as using the SwissPrediction webserver to identify in silico body target proteins of the three statins in mice for possible future exploratory studies, since such information is not available.
Selected References
 1. Rashid HM, Mohammad FK. Differential effects of statins on plasma and brain cholinesterase activities in chicks. Neuroscience Research Notes; 2023, 6(3): 234.1–234.8. doi: 10.31117/neuroscirn.v6i3.234.
2. Rashid HM, Mohammad FK. Statins modify response of chicks to challenges with xylazine-ketamine and carbaryl. Veterinariski Arhiv 2023; 93(4): 463-470.
3. Raouf GA, Mohammad FK, Merza MA. Polypharmacy and the in silico prediction of potential body proteins targeted by these drugs among hospitalized COVID-19 patients with cytokine storm. Cureus 2023; 15(11): e48834. doi:10.7759/cureus.48834.
4. Al-Shalchi RF, Mohammad FK. Oxidative Stress-Induced Adverse Effects of Three Statins Following Single or Repetitive Treatments in Mice. Cureus 2024; 16(1): e51433. DOI 10.7759/cureus.51433
5. Al-Shalchi RF, Mohammad FK. Adverse neurobehavioral changes with reduced blood and brain cholinesterase activities in mice treated with statins. Vet World. 2024; 17(1):82-88.
6. Al-Shalchi RF, Mohammad FK. Changes in propofol anaesthesia and dichlorvos toxicity in mice following repeated dosing with three hypolipidemic statins. Bulgarian Journal of Veterinary Medicine 2024; (in press). (Online first: DOI: 10.15547/bjvm.2024-0002).
7. Al-Shalchi RF, Mohammad FK. Alterations of neurobehavioral performance, blood and brain cholinesterase activities and cholesterol levels by repeated statin treatments in mice. Bulletin of Pharmaceutical Sciences Assiut University 2024; 47(1): 415-425. DOI: 10.21608/BFSA.2024.270145.2033.
8. Al-Shalchi RF, Mohammad FK. In vitro oxidative stress and anticholinesterase effects of atorvastatin, simvastatin and rosuvastatin in the mouse brain. (Submitted).