Alterations of Neurobehavioral Performance, Blood and Brain Cholinesterase Activities and Cholesterol Levels by Repeated Statin Treatments in Mice

Document Type : Original Article

Authors

Department of Physiology, Biochemistry and Pharmacology, College of Veterinary Medicine, University of Mosul, Mosul, Iraq

Abstract

Hypolipidemic statins are characterized by a wide margin of safety, but with adverse effects. The purpose of this study was to further examine and ascertain effects of repeated administrations of atorvastatin, simvastatin and rosuvastatin on neurobehavioral performance, cholinesterase (ChE) activity and cholesterol level in mice. Male Swiss mice were treated orally with each statin at 200 mg/kg of body weight/day for 14- and 28 consecutive days. Control mice were treated with distilled water. Twenty four hours after the last 14- or 28-day dosing, each mouse was tested for 5-min open-field activity, negative geotaxis performance at an angle of 45°, 5-min head pocking and forced swimming endurance. Plasma, erythrocyte and whole brain ChE activities, and plasma and whole brain cholesterol levels were measured. Treatments with each statin for 14 and 28 consecutive days significantly decreased open-field activities and head pocking, and increased the durations of negative geotaxis and forced swimming endurance with reduction of immobility duration. Plasma, erythrocyte and whole brain ChE activities were significantly reduced. The most prominent effect was seen with atorvastatin. Brain ChE activity highly correlated with those of the plasma and erythrocytes. The statins significantly decreased plasma and brain cholesterol levels. The results ascertain adverse behavioral and neuronal cholinergic effects after repeated statin treatments in mice. Considering potential pleiotropic effects, further pharmacological studies are needed to explore values of these changes.

Keywords

Bulletin of Pharmaceutical Sciences Assiut University

Articles in Press, Accepted Manuscript
Available Online from 02 April 2024

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