Al-Shalchi Rawnaq Faris, Mohammad Fouad Kasim
Department of Physiology, Biochemistry and Pharmacology, College of Veterinary Medicine, University of Mosul, Mosul, Iraq.
Vet World. 2024 Jan;17(1):82-88. doi: 10.14202/vetworld.2024.82-88. Epub 2024 Jan 8.
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).
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.
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.
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.
在人类和实验动物中，已表明降血脂他汀类药物具有多效性，对行为结果有影响。关于他汀类药物对小鼠神经行为的影响，相关信息有限。本研究的目的是检测三种常用他汀类药物（阿托伐他汀、辛伐他汀和瑞舒伐他汀）高剂量给药后小鼠神经行为表现和胆碱酯酶（ChE）活性的变化。
在口服给予溶剂（对照）或250、500、750或1000mg/kg他汀类药物两小时后，对每只小鼠进行5分钟旷场活动、以45°/60秒角度的负趋地性、5分钟头部戳刺和强迫游泳耐力测试。在口服给予500和1000mg/kg他汀类药物后2小时和24小时，用分光光度法测定血浆、红细胞和脑ChE活性。
他汀类药物以不同方式，但呈剂量依赖性且显著地（p<0.05）延迟了在旷场区域移动的潜伏期，减少了运动和竖毛行为，降低了头部戳刺行为，并延迟了负趋地性表现。然而，他汀类药物显著增加了强迫游泳的持续时间，并减少了在游泳箱中不动的持续时间。给药后2小时和24小时，他汀类药物显著且呈剂量依赖性地降低了血浆、红细胞和脑ChE活性。24小时后，血浆和脑ChE活性分别从2小时的ChE值恢复了5%-32.9%和5.7%-14.4%。
高剂量他汀类药物与血浆、红细胞和脑ChE活性降低相关，以不同方式调节小鼠的神经行为结果。血浆或红细胞ChE可用于他汀类药物不良/治疗效果的生物监测。
