ABSTRACT
Background and Aim: Pleiotropic effects of hypolipidemic statins with behavioral outcomes have been suggested in humans and laboratory animals. There is limited information on the neurobehavioral effects of statins in mice. The aim of the present study was to examine changes in neurobehavioral performance and cholinesterase (ChE) activity in mice after high doses of three commonly used statins (atorvastatin, simvastatin, and rosuvastatin). Materials and Methods: Two hours after vehicle (control) or statin dosing at 250, 500, 750, or 1000 mg/kg orally, each mouse was subjected to 5 min open-field activity, negative geotaxis at an angle of 45°/60 s, 5 min head pocking, and forced swimming endurance. Plasma, erythrocyte, and brain ChE activities were determined spectrophotometrically 2 and 24 h after oral dosing of statins at 500 and 1000 mg/kg. Results: The statins variably, but dose-dependently and significantly (p < 0.05) delayed the latency to move in the open-field arena, decreased locomotion and rearing, reduced head pocking, and delayed negative geotaxis performance. However, statins significantly increased the duration of forced swimming and decreased the duration of immobility in the swimming tank. Statins significantly and dose-dependently decreased plasma, erythrocyte, and brain ChE activity 2 and 24 h after dosing. Plasma and brain ChE activities recovered by 5%-32.9% and 5.7%-14.4% 24 h later from the 2 h ChE values, respectively. Conclusion: High doses of statins differentially modulate neurobehavioral outcomes in mice in association with reduced plasma, erythrocyte, and brain ChE activity. Plasma or erythrocyte ChE may be used for biomonitoring of the adverse/therapeutic effects of statins.
ABSTRACT
Measurements of blood cholinesterase (ChE) activities, including those of erythrocytes (EChE), plasma or serum (PChE), and whole blood (WBChE), are used to assess exposure to ChE-inhibiting pesticides. The purpose of this review was to report normal reference ChE activities in the blood of healthy adult humans, as determined by a modified electrometric method. We performed a systematic review following PRISMA guidelines. Single-group meta-analysis of means of PChE, EChE, and WBChE activities of adult healthy subjects was conducted using the random effects model. The programs used were Open-Meta Analyst and Meta-Essentials Version 1.5. Studies selected for analysis comprised 21, 19, and 4 reports of normal reference/baseline PChE, EChE, and WBChE activities in 690, 635, and 121 healthy adult males and/or females, respectively. The meta-analysis showed normal reference values of the means (effect sizes) with 95% CI of PChE, EChE, and WBChE activities of healthy adult subjects, which were 1.078 (1.015, 1.142), 1.075 (1.024, 1.125) and 1.331 (1.226, 1.436), respectively. By the subgroup analysis, heterogeneity (I2>89%) was considerably reduced in females to 4.4% and 30.1% for PChE and EChE, respectively. Funnel plots indicated no publication bias. However, Egger's regression confirmed the symmetry of the data points for PChE and WBChE activities with a significant effect on EChE. This meta-analysis showed normal reference values of PChE, EChE, and WBChE activities, measured by a modified electrometric method, in healthy adult humans.
